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Sample records for b16 melanoma transplant

  1. Radiation sensitivity of B-16 melanoma

    International Nuclear Information System (INIS)

    Griem, M.L.; Malkinson, F.D.; Kalis, J.B.; Shefner, A.

    1984-01-01

    A model has been developed for radiation studies of melanoma. Β-16 melanoma (NCI), carried by subcutaneous implant in C57BL/6NCr mice was implanted instramuscularly into the right rear leg of female B6C3F1 mice. Test mice were inoculated with 1 x 10/sup 5/, 5 x 10/sup 5/, and 1 x 10/sup 6/ tumor cells to determine an appropriate tumor challenge for a reproducible and suitable median survival time. A challenge inoculum of 5 x 10/sup 5/ tumor cells was subsequently chosen as the standard tumor dose for test animals used in subsequent radiation dose response studies. Tumor-bearing test animals were treated with 500, 1000, 1500, or 2000 rads of 250 kV x-rays either 4 days or 14 days after tumor implantation. Only the tumorbearing leg of the test mouse was exposed during irradiation; the animal was otherwise protected by lead shielding. The median survival time of tumorbearing unirradiated mice was 24.4 days. Radiation on day 4 postinoculation was more effective than radiation administered on day 14. Median survival time for the 4 radiation dose groups given x-rays on day 4 were 31.0, 38.2, 59.0, and 60.0 days with progressive increases in radiation dose. Median survival times for mice irradiated on day 14 were 26.8, 31.8, 34.8, and 49.2 days as the radiation doses increased. This mouse melanoma model can be used in combined modality studies

  2. Cathepsin L increases invasion and migration of B16 melanoma

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    Cox James L

    2007-05-01

    Full Text Available Abstract Background Most cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth, metastatic spread, and angiogenesis. Elevation of the cathepsins of the cysteine protease family correlates with increased invasion of tumor cells. Cysteine proteases such as cathepsins B, H and L type participate in tumor cell invasion as extracellular proteases, yet are enzymes whose exact roles in metastasis are still being elucidated. Methods We have examined the role of cathepsin L in highly metastatic B16F10 murine melanoma cells through genetic antisense constructs of cathepsin L. The effects of cathepsin L antisense were examined for melanoma cell proliferation, invasion, migration and adhesion. Results Antisense expression of cathepsin L, while decreasing enzyme activity in cell lysates, did not influence cell proliferation. Cathepsin L contributed to melanoma cell invasion and also augmented melanoma cell migration. Further, we demonstrated the adhesion of cathepsin L down-regulated clones was unaltered to fibronectin, laminin, and collagen. Finally, the inhibition of melanoma cell migration via down-regulation of cathepsin L appears to be independent of cystatin C expression. Conclusion This study shows that cathepsin L facilitates high metastatic B16 melanoma cell invasion and migration. The mechanism of migration inhibition by decreased cathepsin L is independent of cystatin C levels. Since metastasis depends upon both the invasiveness and migration of tumor cells, cathepsin L may be a therapeutic target of strong clinical interest.

  3. Effect of selenium compounds on murine B16 melanoma cells and pigmented cloned pB16 cells

    International Nuclear Information System (INIS)

    Siwek, B.; Bahbouth, E.; Serra, M.A.; Sabbioni, E.; Pauw-Gillet, M.C. de; Bassleer, R.

    1994-01-01

    The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 μM and 10 μM) on B16 and pigmented cloned pB 16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB 16 cells, whereas no decrease of B 16 and pB 16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B 16 than in pB 16 cells. The pretreatment of B 16 cells with a GSH depleting agent (10 μM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations. GSH preincubation (50 μM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B 16 cells was more sensitive than in pB 16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine; however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75 Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75 Se in cytosol and pellet was approximately the same. Gel filtration chromatography of lysed cells after incubation for 6 h with 10 μM 75 Se-selenite showed that the radioactivity was eluted as two peaks corresponding to low (4-9 kDa) and high (280-320 kDa) molecular weights. Possible toxicological mechanisms are discussed at molecular level. (orig./MG)

  4. Protective immunization with B16 melanoma induces antibody response and not cytotoxic T cell response

    International Nuclear Information System (INIS)

    Sarzotti, M.; Sriyuktasuth, P.; Klimpel, G.R.; Cerny, J.

    1986-01-01

    C57BL/6 mice immunized with three intraperitoneal injections of syngeneic, irradiated B16 melanoma cells, became resistant to B16 tumor challenge. Immunized mice had high levels of serum antibody against a membrane antigen of B16 cells. The B16 antigen recognized by the anti-B16 sera formed a major band of 90 KD in gel electrophoresis. The anti-B16 antibody was partially protective when mixed with B16 cells and injected into normal recipient mice. Surprisingly, B16 resistance mice were incapable of generating cytotoxic T cells (CTL) specific for the B16 tumor. Both spleen and lymph node cell populations from immunized mice did not generate B16-specific CTL. Allogeneic mice (DBA/2 or C3H) were also unable to generate B16-specific CTL: however, alloreactive CTL produced in these strains of mice by immunization with C57BL/6 lymphocytes, did kill B16 target cells. Interestingly, spleen cells from syngeneic mice immunized with B16 tumor produced 6-fold more interleukin-2 (IL-2) than normal spleen cells, in vitro. These data suggest that immunization with B16 tumor activates a helper subset of T cells (for antibody and IL-2 production) but not the effector CTL response

  5. Effect of Chlorogenic Acid on Melanogenesis of B16 Melanoma Cells

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    Hao-Rong Li

    2014-08-01

    Full Text Available Chlorogenic acid (CGA, the ester formed between caffeic acid and l-quinic acid, is a widespread phenolic compound. It is part of the human diet, found in foods such as coffee, apples, pears, etc. CGA is also was widely used in cosmetics, but the effects of CGA on melanogenesis are unknown. In this study, we analyzed the effects of CGA on cell proliferation, melanin content and tyrosinase of B16 murine melanoma cells. Additionally, the enzymatic reactions of CGA in B16 melanoma cells lytic solution were detected by UV spectrophotometry. Results showed CGA at 30 and 60 μM significantly suppresses cell proliferation. 8-MOP at 100 μM significantly promotes cell proliferation, but CGA can counter this. Incubated for 24 h, CGA (500 μM improves melanogenesis while suppressing tyrosinase activity in B16 melanoma cells or 8-methoxypsoralen (8-MOP co-incubated B16 melanoma cells. After 12 h, B16 melanoma cell treatment with CGA leads to an increase in melanin accumulation, however, after 48 h there is a decrease in melanin production which correlates broadly with a decrease in tyrosinase activity. CGA incubated with lytic solution 24 h turned brown at 37 °C. The formation of new products (with a maximum absorption at 295 nm is associated with reduction of CGA (maximum absorption at 326 nm. Therefore, CGA has its two sidesroles in melanogenesis of B16 melanoma cells. CGA is a likely a substrate of melanin, but the metabolic product(s of CGA may suppress melanogenesis in B16 melanoma cells by inhibiting tyrosinase activity.

  6. Oncogenesis of melanoma B16 cell clones mutagenized by space environment

    International Nuclear Information System (INIS)

    Guo Yupeng; Yang Hongsheng; Tang Jingtian; Xu Mei; Geng Chuanying; Fang Qing; Xu Bo; Li Hongyan; Xiang Xing; Pan Lin

    2005-01-01

    Objective: To explore the oncogenesis of the melanoma B16 cell clones mutagenized by space environment, and find the B16 cell clones with remarkably mutated immunogenicity. Methods: B16 cells were carried by the Chinese 20th recoverable satellite to the outer space, and were harvested after 18 days' spaceflight and then monocloned. Four cell clones, which were randomly selected from the total 110 clones obtained , and the control clone were routinely cultured. The cultured cells were injected to 10 groups of C57BL/6J mice, 82.1 mice in each group. Five groups of mice received hypodermic injection and another 5 groups of mice received abdominal injection. The survival time was observed in abdominal injection groups. The mice in hypodermic injection groups were sacrificed after 14 days, the tumor, spleen and thymus were weighted, and the serum IL-2 concentration was determined. Moreover, the melanoma tumor tissues were examined histopathologically. Results: An experiment program suitable to screening space mutagenesis of B16 tumor cell clones in vivo and the observation indices were basically established. One clone was found out which was remarkably different from the control clone in latent period of tumor formation, tumor weight, survival time of the tumor-bearing mice and the expression of IL-2. Conclusions: Cultured melanoma B16 cells could be mutated by outer space environment. The further study will be focused on the influence of space environment on immunogenicity of mutagenized B16 cells. (authors)

  7. Effect of fucoidan on B16 murine melanoma cell melanin formation ...

    African Journals Online (AJOL)

    Background:Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. It not only inhibits cancer cell growth but also inhibits tyrosinase in vitro. Therefore, it is of interest to investigate the effect of fucoidan on B16 murine melanoma cells as the findings may ...

  8. Efficient treatment of pigmented B16 melanoma using photosensitized long-circulating magnetofullerenosomes

    International Nuclear Information System (INIS)

    Babinec, Peter; Babincova, Melania; Sourivong, Paul; Leszczynska, Danuta

    2005-01-01

    Magnetic targeting was used for melanoma treatment with magnetofullerenosomes. After their intravenous administration, a permanent magnet was attached to the surface of B16 tumors in C57 mice for 24 h, followed by irradiation with an infrared laser pulse and subsequent illumination with a 776 nm diode laser for conventional photodynamic treatment. Tumor response was substantially better than that obtained with either treatment alone

  9. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

    OpenAIRE

    Kranjc Simona; Kranjc Matej; Scancar Janez; Jelenc Jure; Sersa Gregor; Miklavcic Damijan

    2016-01-01

    Introduction Pulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Materials and methods Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intrave...

  10. DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes

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    Panpen Diawpanich

    2008-07-01

    Full Text Available Media components may affect the activities of cultured cells. In this study, tyrosinase activity was evaluated by using B16-F10 mouse melanoma cell lines (B16-F10 and primary human melanocytes cultured in different media. An optical density measurement and a L-dopa reaction assay were used as the determination of the tyrosinase activity. The study of B16-F10 found the optical density to be 2010, 2246 and 2961 in cells cultured in RPMI Medium 1640 (RPMI1640,Minimum Essential Medium (MEM and Dulbecco’s Modified Eagle Medium (DMEM, respectively. Moreover, compared to RPMI 1640 and MEM, DMEM showed the darkest color of melanin formation in culture media and in cells after the L-dopa reaction assay. Addition of kojic acid showed a significant inhibitory effect on tyrosinase activity in all media.Whereas MCDB153 showed no significant effect on human melanocytes, DMEM caused a dramatic increase in tyrosinase activity after 4 days of cultivation. Addition of kojic acid showed a significant tyrosinase inhibitory effect in DMEM only. Furthermore, an active ingredient in green tea, epigallocathechin gallate (EGCG could inhibit tyrosinase activity in both B16-F10 and human melanocytes cultured in DMEM. In summary, these results suggest that DMEM is a suitable medium that provides high detection sensitivity in a tyrosinase inhibition assay.

  11. Melanogenesis inhibits respiration in B16-F10 melanoma cells whereas enhances mitochondrial cell content

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    Meira, Willian Vanderlei; Heinrich, Tassiele Andréa; Cadena, Silvia Maria Suter Correia; Martinez, Glaucia Regina, E-mail: grmartinez@ufpr.br

    2017-01-01

    Melanoma is a rare and aggressive skin tumor; the survival of patients diagnosed late is fairly low. This high mortality rate is due to the characteristics of the cells that allow them to be resistant to radiotherapy and conventional chemotherapy, besides of being able to evade the immune system. Melanin, the pigment responsible for skin, hair and eye color, seems to be involved in this resistance. The main function of melanin is to protect the cells against ultraviolet (UV) light by absorbing this radiation and reactive oxygen species (ROS) scavenging. But this pigment may have also a role as photosensitizer, because when it is irradiated with UVA light (320-400 nm), the generation of ROS was detected. Besides, the melanogenesis stimulation on B16-F10 cells resulted in cell cycle arrest, induction of a quiescent state, change in the expression of several proteins and alterations on ADP/ATP ratio. The present study aimed to investigate the influence of melanogenesis stimulation in mitochondrial function of B16-F10 melanoma cells. Therefore, we analyzed cells respiration, mitochondrial membrane potential (Δψ{sub m}) and mitochondria mass in B16-F10 melanoma cells stimulated with 0.4 mM L-tyrosine and 10 mM NH{sub 4}Cl. Our results showed that the induction of melanin synthesis was able to reduce significantly the oxygen consumption after 48 h of stimulation, without changes of mitochondrial membrane potential when compared to non-stimulated cells. Despite of respiration inhibition, the mitochondria mass was higher in cells with melanogenesis stimulation. We suggest that the stimulation in the melanin synthesis might be promoting the inhibition of electrons transport chain by some intermediate compound from the synthesis of the pigment and this effect could contribute to explain the entry in the quiescent state. - Highlights: • Melanoma pigmentation alters mitochondrial respiration. • Induction of melanin synthesis by 48 h do not change mitochondrial membrane

  12. A galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse B16 melanoma.

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    Hou, Chia-Chung; Chen, Yi-Ping; Wu, Jyh-Horng; Huang, Chi-Chang; Wang, Sheng-Yang; Yang, Ning-Sun; Shyur, Lie-Fen

    2007-07-15

    Crassocephalum rabens (Asteraceae) is a popular anti-inflammatory folk medicine and food supplement. We investigated the cancer chemopreventive bioactivity of C. rabens phytocompounds in vitro and in vivo using cell- and gene-based bioassays and a mouse B16 melanoma model. The bioactive glyceroglycolipid 1,2-di-O-alpha-linolenoyl-3-O-beta-galactopyranosyl-sn-glycerol (dLGG) that was identified from C. rabens was found in vitro and in vivo to be a potent nitric oxide (NO) scavenger. dLGG treatment inhibited both mRNA and protein expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in murine macrophages and inhibited COX-2 gene transcription in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B16 cells. In immunohistochemical studies, dLGG inhibited TPA-induced expression of COX-2 and nitration of proteins in mouse skin. dLGG could also significantly inhibit lipopolysaccharide-induced prostaglandin E(2) production in murine macrophages. Furthermore, dLGG prevented nuclear translocation of cytoplasmic nuclear factor-kappaB (NF-kappaB) by suppressing IkappaBalpha phosphorylation and degradation. Structure-activity relationship study by electrophoretic mobility shift assay indicated that the dilinolenoylglycerol moiety in dLGG is the essential structural feature preventing NF-kappaB.DNA complex formation. A dLGG-enriched extract from C. rabens (10 mg/kg) markedly suppressed B16 melanoma growth in C57BL/6J mice following i.p. administration, an effect comparable with that of cisplatin, a cancer chemotherapeutic drug. This study shows the detailed molecular mechanism(s) underlying the anti-inflammatory and tumor-suppressive effects of a natural galactolipid.

  13. Protein kinase Calpha plays a critical role in mannosylerythritol lipid-induced differentiation of melanoma B16 cells.

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    Zhao, X; Murata, T; Ohno, S; Day, N; Song, J; Nomura, N; Nakahara, T; Yokoyama, K K

    2001-10-26

    Mannosylerythritol lipid (MEL), a novel extracellular glycolipid from yeast, was found to inhibit the proliferation of mouse melanoma B16 cells in a dose-dependent manner and to induce the apoptosis of B16 cells at concentrations higher than 10 microm (Zhao, X., Wakamatsu, Y., Shibahara, M., Nomura, N., Geltinger, C., Nakahara, T., Murata, T., and Yokoyama, K. K. (1999) Cancer Res. 59, 482-486). We show here that exposure of B16 cells to MEL (5 microm) for 2 days resulted in an increase of the levels of differentiation-associated markers of melanoma cells such as melanogenesis and tyrosinase activity, which were accompanied by morphological changes. The MEL-induced differentiation of B16 cells at this concentration was closely associated with arrest of the cell cycle at G(1) phase, but no significant population of apoptotic cells was identified. Expression of protein kinase Calpha (PKCalpha) was enhanced after exposure of B16 cells to MEL for 48 h. Antisense oligodeoxynucleotides against the mouse gene for PKCalpha prevented MEL-induced melanogenesis in B16 cells. Conversely, the effects of the expression of a constitutively active form of PKCalpha mimicked the effects of MEL on B16 cells. These data suggest that MEL, a yeast-derived glycolipid, triggers the differentiation of B16 melanoma cells through a signaling pathway that involves PKCalpha.

  14. Non-malignant migration of B16 mouse melanoma cells in the neural crest and invasive growth in the eye cup of the chick embryo.

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    Oppitz, Matthias; Busch, Christian; Schriek, Gernot; Metzger, Marco; Just, Lothar; Drews, Ulrich

    2007-02-01

    Melanocytes originate from the neural crest. In a previous study, we observed that human SK-Mel 28 human melanoma cells resumed neural crest cell migration after transplantation into the chick embryo neural tube. Here, we used transgenic mouse B16-F1 melanoma cells transfected with green fluorescent protein-vasodilator-stimulated phosphoprotein construct to extend these observations. After the injection of a cell suspension into the trunk neural tube of E2 chick embryos, the migration of melanoma cells was followed by live fluorescence microscopy. Within 12 h, the melanoma cells formed clusters in the neural tube at the levels of the intersegmental clefts between somites. After 24 h, a segmental pattern of emigration was visible. Emigrated melanoma cells were identified in serial paraffin sections by immunohistochemistry with ab732 as a marker for melanoma cells and by in-situ hybridization of mouse-specific repetitive genomic sequence mL1. After 24 h, melanoma cells were found along the medial neural crest pathway and in the sympathetic trunk ganglia and, after 48 h, also in the lateral melanocytic pathway. During migration along the neural crest pathways, mouse melanoma cells underwent apoptosis, which was assessed by anti-caspase 3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining. To prove the ablation of malignant behavior after back-transplantation into the original embryonic neural crest environment, we injected the same cell suspension into the eye cup of the E3 embryo. In this location, invasive melanomas formed.

  15. Atmospheric-pressure plasma jet characterization and applications on melanoma cancer treatment (B/16-F10)

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    Mashayekh, Shahriar; Rajaee, Hajar; Akhlaghi, Morteza; Shokri, Babak; Hassan, Zuhir M.

    2015-09-01

    A new approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper, a pin-to-hole plasma jet for biological applications has been designed and manufactured and characterized. The characterization includes power consumption via Lissajous method, thermal behavior of atmospheric-pressure plasma jet by using Infra-red camera as a novel method and using Speicair software to determine vibrational and transitional temperatures, and optical emission spectroscopy to determine the generated species. Treatment of Melanoma cancer cells (B16/F10) was also implemented, and tetrazolium salt dye (MTT assay) and flow cytometry were used to evaluate viability. Effect of ultraviolet photons on cancerous cells was also observed using an MgF2 crystal with MTT assay. Finally, in-vivo studies on C57 type mice were also done in order to have a better understanding of the effects in real conditions.

  16. Atmospheric-pressure plasma jet characterization and applications on melanoma cancer treatment (B/16-F10)

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    Mashayekh, Shahriar [Physics Department, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Rajaee, Hajar; Hassan, Zuhir M. [Imonology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran (Iran, Islamic Republic of); Akhlaghi, Morteza [Laser-Plasma Research Institute, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Shokri, Babak [Physics Department and Laser-Plasma Research Institute, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of)

    2015-09-15

    A new approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper, a pin-to-hole plasma jet for biological applications has been designed and manufactured and characterized. The characterization includes power consumption via Lissajous method, thermal behavior of atmospheric-pressure plasma jet by using Infra-red camera as a novel method and using Speicair software to determine vibrational and transitional temperatures, and optical emission spectroscopy to determine the generated species. Treatment of Melanoma cancer cells (B16/F10) was also implemented, and tetrazolium salt dye (MTT assay) and flow cytometry were used to evaluate viability. Effect of ultraviolet photons on cancerous cells was also observed using an MgF{sub 2} crystal with MTT assay. Finally, in-vivo studies on C57 type mice were also done in order to have a better understanding of the effects in real conditions.

  17. Depigmenting mechanism of NSAIDs on B16F1 melanoma cells.

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    Sato, Kazuomi; Takahashi, Hideki; Toriyama, Masaru

    2011-04-01

    The aim of the present work was to clarify the anti-melanogenic mechanism of non-steroidal anti-inflammatory drugs (NSAIDs). Mefenamic acid, diclofenac, and nimesulide were used in this study, and these drugs inhibit melanin synthesis in B16F1 melanoma cells. To elucidate the anti-melanogenic mechanism of NSAIDs, we performed western blotting analysis for melanogenic proteins, such as tyrosinase, TRP-1, and TRP-2. All NSAIDs used in this study inhibited tyrosinase protein level. Semi-quantitative RT-PCR analysis showed that the depigmentation effect of mefenamic acid and nimesulide might be due to the inhibition of tyrosinase gene transcription. These results indicate that NSAIDs inhibit α-MSH-enhanced melanin synthesis, and are candidate anti-melanogenic agents since they might be effective in hyperpigmentation disorders.

  18. Evaluation of Depigmenting Activity by 8-Hydroxydaidzein in Mouse B16 Melanoma Cells and Human Volunteers

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    Ching-Gong Lin

    2009-09-01

    Full Text Available In our previous study, 8-hydroxydaidzein (8-OHDe was demonstrated to be a potent and unique suicide substrate of mushroom tyrosinase. In this study, the compound was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in human volunteers. Tyrosinase activity and melanogenesis in the cell culture incubated with 10 µM of 8-OHDe were decreased to 20.1% and 51.8% of control, respectively, while no obvious cytotoxicity was observed in this concentration. In contrast, a standard tyrosinase inhibitor, kojic acid, showed 69.9% and 71.3% of control in cellular tyrosinase and melanogenesis activity, respectively, at a concentration as high as 100 µM. Hence, 8-OHDe exhibited more than an inhibitory effects on melanin production in B16 cells 10-fold stronger than kojic acid. In addition, when a cream containing 4% 8-OHDe was applied to human skin in an in vivo study, significant increases in the dL*-values were observed after three weeks. Moreover, the increase in the dL*-values after 8-week treatment with 4% 8-OHDe (from -0.57 to 1.94 is stronger than those of 2% 8-OHDe treatment (from 0.26 to 0.94 and 2% ascorbic acid-2-glucoside treatment (from 0.07 to 1.54. From the results of the study, it was concluded that 8-OHDe, the potent suicide substrate of mushroom tyrosinase, has depigmenting activities in both mouse melanoma cells and in human volunteers. Thus, the compound has significant potential for use in cosmetics as a skin-whitening ingredient.

  19. Radiation Changes the Metabolic Profiling of Melanoma Cell Line B16.

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    Lige Wu

    Full Text Available Radiation therapy can be an effective way to kill cancer cells using ionizing radiation, but some tumors are resistant to radiation therapy and the underlying mechanism still remains elusive. It is therefore necessary to establish an appropriate working model to study and monitor radiation-mediated cancer therapy. In response to cellular stress, the metabolome is the integrated profiling of changes in all metabolites in cells, which can be used to investigate radiation tolerance mechanisms and identify targets for cancer radiation sensibilization. In this study, using 1H nuclear magnetic resonance for untargeted metabolic profiling in radiation-tolerant mouse melanoma cell line B16, we comprehensively investigated changes in metabolites and metabolic network in B16 cells in response to radiation. Principal component analysis and partial least squares discriminant analysis indicated the difference in cellular metabolites between the untreated cells and X-ray radiated cells. In radiated cells, the content of alanine, glutamate, glycine and choline was increased, while the content of leucine, lactate, creatine and creatine phosphate was decreased. Enrichment analysis of metabolic pathway showed that the changes in metabolites were related to multiple metabolic pathways including the metabolism of glycine, arginine, taurine, glycolysis, and gluconeogenesis. Taken together, with cellular metabolome study followed by bioinformatic analysis to profile specific metabolic pathways in response to radiation, we deepened our understanding of radiation-resistant mechanisms and radiation sensibilization in cancer, which may further provide a theoretical and practical basis for personalized cancer therapy.

  20. Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells

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    Katarina Znidar

    2016-01-01

    Full Text Available In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNβ mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16.F10 cells in culture, IFNβ mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA-dependent activator of interferon regulatory factor (DAI, DEAD (Asp-Glu-Ala-Asp box polypeptide 60 (DDX60, and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16.F10 cells, inducing effects in vitro and potentially in vivo.

  1. B16F1 melanoma cells upregulate melanin synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Moder, A.; Gassner, F.; Krammer, B.; Thalhamer, J.; Hammerl, P.

    2003-01-01

    Full text: The success of photodynamic therapy (PDT) of melanotic tumors is severely limited by insufficient penetration of light into deeper tissue layers. In this study, we analyzed the effect of PDT on the melanin production of the melanoma cell line B16F1. In vitro, these cells produce only little melanin. However, after PDT we found a dramatic elevation in intracellular melanin. Melanin production increased with, both, the concentration of the sensitizing agent and the light dose, and was found to continue for several hours after cell death. PDT-induced melanin synthesis was not prevented by the addition of cycloheximide or actinomycin D prior to irradiation, indicating that de-novo protein synthesis and transcriptional activity are not required for this effect. We also analyzed tyrosinase activity, a key enzyme in melanin biosynthesis, in PDT-treated B16 cells. Tyrosinase activity was found in PDT-treated as well as untreated cells. Cell fractionation experiments showed that tyrosinase was present in the cytosolic as well as the melanosomal fractions of, both, PDT-treated (melanin-high) as well as untreated (melanin-low) cells. These data indicate that PDT-induced production of melanin is not controlled at the transcriptional or translational level and that tyrosinase is not likely an essential regulator in this process. (author)

  2. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol.

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    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-06-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.

  3. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    International Nuclear Information System (INIS)

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-01-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

  4. B16 melanoma tumor growth is delayed in mice in an age-dependent manner

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2012-08-01

    Full Text Available A major risk factor for cancer is increasing age, which suggests that syngeneic tumor implants in old mice would grow more rapidly. However, various reports have suggested that old mice are not as permissive to implanted tumor cells as young mice. In order to determine and characterize the age-related response to B16 melanoma, we implanted 5×105 tumor cells into 8, 16, 24, and 32-month-old male C57BL/6 (B6 and C57BL/6×BALB/c F1 (CB6 F1 mice subcutaneously in the inguinal and axillary spaces, or intradermally in the lateral flank. Results showed decreased tumor volume with increasing age, which varied according to mouse genetic background and the implanted site. The B6 strain showed robust tumor growth at 8 months of age at the inguinal implantation site, with an average tumor volume of 1341.25 mm3. The 16, 24, and 32-month age groups showed a decrease in tumor growth with tumor volumes of 563.69, 481.02, and 264.55 mm3, respectively (p≤0.001. The axillary implantation site was less permissive in 8-month-old B6 mice with an average tumor volume of 761.52 mm3. The 24- and 32-month age groups showed a similar decrease in tumor growth with tumor volumes of 440 and 178.19 mm3, respectively (p≤0.01. The CB6F1 strain was not as tumor permissive at 8 months of age as B6 mice with average tumor volumes of 446.96 and 426.91 mm3 for the inguinal and axillary sites, respectively. There was a decrease in tumor growth at 24 months of age at both inguinal and axillary sites with an average tumor volume of 271.02 and 249.12 mm3, respectively (p≤0.05. The strain dependence was not apparent in 8-month-old mice injected intradermally with B16 melanoma cells, with average tumor volumes of 736.82 and 842.85 mm3 for B6 and CB6 F1, respectively. However, a strain difference was seen in 32-month-old B6 mice with an average decrease in tumor volume of 250.83 mm3 (p≤0.01. In contrast, tumor growth significantly decreased earlier in CB6 F1 mice with average

  5. Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation.

    Science.gov (United States)

    Tabolacci, Claudio; Rossi, Stefania; Lentini, Alessandro; Provenzano, Bruno; Turcano, Lorenzo; Facchiano, Francesco; Beninati, Simone

    2013-01-01

    Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity. To improve the growth-inhibiting effect of anticancer agents, we found that the combined treatment of cells with aloin and low doses of cisplatin increases the antiproliferative activity of aloin. The results suggest that aloin possesses antineoplastic and antimetastatic properties, exerted likely through the induction of melanoma cell differentiation.

  6. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo.

    Science.gov (United States)

    Kranjc, Simona; Kranjc, Matej; Scancar, Janez; Jelenc, Jure; Sersa, Gregor; Miklavcic, Damijan

    2016-03-01

    Pulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intravenously injection of cisplatin (CDDP) (4 mg/kg), PEMF (480 bipolar pulses, at frequency of 80 Hz, pulse duration of 340 μs) or with the combination of both therapies (electrochemotherapy - PEMF + CDDP). Antitumor effectiveness of treatments was evaluated by tumor growth delay assay. In addition, the platinum (Pt) uptake in tumors and serum, as well as Pt bound to the DNA in the cells and Pt in the extracellular fraction were measured by inductively coupled plasma mass spectrometry. The antitumor effectiveness of electrochemotherapy with CDDP mediated by PEMF was comparable to the conventional electrochemotherapy with CDDP, with the induction of 2.3 days and 3.0 days tumor growth delay, respectively. The exposure of tumors to PEMF only, had no effect on tumor growth, as well as the injection of CDDP only. The antitumor effect in combined treatment was related to increased drug uptake into the electroporated tumor cells, demonstrated by increased amount of Pt bound to the DNA. Approximately 2-fold increase in cellular uptake of Pt was measured. The obtained results in mouse melanoma model in vivo demonstrate the possible use of PEMF induced electroporation for biomedical applications, such as electrochemotherapy. The main advantages of electroporation mediated by PEMF are contactless and painless application, as well as effective electroporation compared to conventional electroporation.

  7. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

    International Nuclear Information System (INIS)

    Kranjc, Simona; Kranjc, Matej; Scancar, Janez; Jelenc, Jure; Sersa, Gregor; Miklavcic, Damijan

    2016-01-01

    Pulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intravenously injection of cisplatin (CDDP) (4 mg/kg), PEMF (480 bipolar pulses, at frequency of 80 Hz, pulse duration of 340 μs) or with the combination of both therapies (electrochemotherapy − PEMF + CDDP). Antitumor effectiveness of treatments was evaluated by tumor growth delay assay. In addition, the platinum (Pt) uptake in tumors and serum, as well as Pt bound to the DNA in the cells and Pt in the extracellular fraction were measured by inductively coupled plasma mass spectrometry. The antitumor effectiveness of electrochemotherapy with CDDP mediated by PEMF was comparable to the conventional electrochemotherapy with CDDP, with the induction of 2.3 days and 3.0 days tumor growth delay, respectively. The exposure of tumors to PEMF only, had no effect on tumor growth, as well as the injection of CDDP only. The antitumor effect in combined treatment was related to increased drug uptake into the electroporated tumor cells, demonstrated by increased amount of Pt bound to the DNA. Approximately 2-fold increase in cellular uptake of Pt was measured. The obtained results in mouse melanoma model in vivo demonstrate the possible use of PEMF induced electroporation for biomedical applications, such as electrochemotherapy. The main advantages of electroporation mediated by PEMF are contactless and painless application, as well as effective electroporation compared to conventional electroporation

  8. Anti-Melanogenic Property of Geoditin A in Murine B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Chun-Tao Che

    2012-02-01

    Full Text Available Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and human colon HT29 cancer cells through an oxidative stress, a process also interfering with normal melanogenesis in pigment cells. Treatment of murine melanoma B16 cells with geoditin A decreased expression of melanogenic proteins and cell melanogenesis which was aggravated with adenylate cyclase inhibitor SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent signaling pathway. Immunofluorescence microscopy and glycosylation studies revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and tyrosinase-related protein 1, and a co-localization of tyrosinase with calnexin (CNX and lysosome-associated membrane protein 1 (LAMP-1, implicating a post-translational modification in the ER and a degradation of tyrosinase in the lysosome. Taken together, potent anti-melanogenic property and the relatively low cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin lightening agent.

  9. Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice

    Directory of Open Access Journals (Sweden)

    Fabrício A. Voltarelli

    2017-09-01

    Full Text Available Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6 and lactate dehydrogenase (LDH activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

  10. Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells.

    OpenAIRE

    Matthew, E; Laskin, J D; Zimmerman, E A; Weinstein, I B; Hsu, K C; Engelhardt, D L

    1981-01-01

    We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein-labeled protein. Our studies also showed tha...

  11. Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

    Energy Technology Data Exchange (ETDEWEB)

    Beninati, Simone, E-mail: beninati@bio.uniroma2.it [Department of Biology, University “Tor Vergata”, Rome (Italy); Oliverio, Serafina [Department of Biology, University “Tor Vergata”, Rome (Italy); Cordella, Martina [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy); Rossi, Stefania; Senatore, Cinzia [Regina Elena National Cancer Institute, Rome (Italy); Liguori, Immacolata; Lentini, Alessandro; Piredda, Lucia [Department of Biology, University “Tor Vergata”, Rome (Italy); Tabolacci, Claudio [Department of Biology, University “Tor Vergata”, Rome (Italy); Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy)

    2014-08-08

    Highlights: • We studied the anticancer potential of a new emerging molecule, α-mangostin (α-M). • We provide first evidences on the effects of α-M on transglutaminase activity. • We deeply examined the antimetastatic effects of α-M through many in vitro assays. • Proteomic analysis revealed that α-M promotes a reorganization at cellular level. - Abstract: In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma.

  12. Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline.

    Science.gov (United States)

    Gude, R P; Binda, M M; Presas, H L; Klein-Szanto, A J; Bonfil, R D

    1999-01-01

    Pentoxifylline (PTX), a methylxanthine derivative widely used as a hemorheological agent in the treatment of peripheral vascular disease, was studied to unveil the mechanisms responsible for its inhibitory action on B16-F10 experimental metastasis. In vitro pretreatment of B16-F10 cells with noncytotoxic concentrations of PTX significantly inhibited their adhesion to reconstituted basement membrane Matrigel(R) and type IV collagen as well as the relative activity of secreted 92 kD metalloproteinase. However, PTX pretreatment of B16-F10 cells did not affect their in vitro invasiveness. Heterotypic organ adhesion assays carried out with B16-F10 cells and suspended organ tissues demonstrated that pretreatment with noncytotoxic concentrations of PTX of both, tumor cells or lung tissue, brought about a dose-dependent inhibition of melanoma cell adhesion to lung. Immunohistochemical studies using antibodies against CD31 adhesion molecule (PECAM-1) revealed that B16-F10 cells adhere to lung endothelial cells. Our results suggest that PTX may exert its inhibitory effect on tumor lodgment, and as a consequence of that on experimental metastases, through an inhibitory action on cell adhesion molecules.

  13. C5 Extract Induces Apoptosis in B16F10 Murine Melanoma Cells ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-cancer activities of C5 extract (C5E), a new herbal preparation from Korea, on B16F10 cells. Methods: The anti-proliferative effects of C5E were assessed by culturing B16F10 cells in the presence or absence of C5E. Cell cycle progression was analyzed by PI staining using flow cytometry.

  14. Anticancer Activity of Saponins from Allium chinense against the B16 Melanoma and 4T1 Breast Carcinoma Cell.

    Science.gov (United States)

    Yu, Zhihui; Zhang, Tong; Zhou, Fengjuan; Xiao, Xiuqing; Ding, Xuezhi; He, Hao; Rang, Jie; Quan, Meifang; Wang, Ting; Zuo, Mingxing; Xia, Liqiu

    2015-01-01

    The cytotoxic substance of A. chinense saponins (ACSs) was isolated using ethanol extraction and purified with the D101 macroporous adsorption resin approach. We investigated the anticancer activity of ACSs in the B16 melanoma and 4T1 breast carcinoma cell lines. Methylthioninium chloride and hematoxylin-eosin staining with Giemsa dyestuff were used when the cells were treated with ACSs. The results showed that the cells morphologies changed significantly; ACSs induced cell death in B16 and 4T1 cells based on acridine orange/ethidium bromide double fluorescence staining, with the number and degree of apoptotic tumor cells increasing as ACS concentration increased. ACSs inhibited the proliferation of B16 and 4T1 cells in a dose-dependent manner. They also inhibited cell migration and colony formation and exhibited a concentration-dependent effect. In addition, ACSs apparently inhibited the growth of melanoma in vivo. The preliminary antitumor in vivo assay revealed that early medication positively affected tumor inhibition action and effectively protected the liver and spleen of C57 BL/6 mice from injury. This study provides evidence for the cytotoxicity of ACSs and a strong foundation for further research to establish the theoretical basis for cell death and help in the design and development of new anticancer drugs.

  15. Anticancer Activity of Saponins from Allium chinense against the B16 Melanoma and 4T1 Breast Carcinoma Cell

    Directory of Open Access Journals (Sweden)

    Zhihui Yu

    2015-01-01

    Full Text Available The cytotoxic substance of A. chinense saponins (ACSs was isolated using ethanol extraction and purified with the D101 macroporous adsorption resin approach. We investigated the anticancer activity of ACSs in the B16 melanoma and 4T1 breast carcinoma cell lines. Methylthioninium chloride and hematoxylin-eosin staining with Giemsa dyestuff were used when the cells were treated with ACSs. The results showed that the cells morphologies changed significantly; ACSs induced cell death in B16 and 4T1 cells based on acridine orange/ethidium bromide double fluorescence staining, with the number and degree of apoptotic tumor cells increasing as ACS concentration increased. ACSs inhibited the proliferation of B16 and 4T1 cells in a dose-dependent manner. They also inhibited cell migration and colony formation and exhibited a concentration-dependent effect. In addition, ACSs apparently inhibited the growth of melanoma in vivo. The preliminary antitumor in vivo assay revealed that early medication positively affected tumor inhibition action and effectively protected the liver and spleen of C57 BL/6 mice from injury. This study provides evidence for the cytotoxicity of ACSs and a strong foundation for further research to establish the theoretical basis for cell death and help in the design and development of new anticancer drugs.

  16. LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor.

    Directory of Open Access Journals (Sweden)

    Maikel Jongsma

    Full Text Available Lysophosphatidic acid (LPA, a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA(1-6, showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18:1 being 10-fold more potent than acyl-LPA(18:1. The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA(2, LPA(5 and LPA(6 receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA(5 receptor (GPR92, which raises intracellular cAMP via a noncanonical pathway. Our results define LPA(5 as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.

  17. Tectona grandis leaf extract, free and associated with nanoemulsions, as a possible photosensitizer of mouse melanoma B16 cell.

    Science.gov (United States)

    de Menezes Furtado, Cydia; de Faria, Fernando Sergio Escocio Drumond Viana; Azevedo, Ricardo Bentes; Py-Daniel, Karen; Dos Santos Camara, Ana Lygia; da Silva, Jaqueline Rodriguez; de Holanda Oliveira, Everton; Rodriguez, Anselmo Fortunato Ruiz; Degterev, Igor Anatolievich

    2017-02-01

    Over the past six years we have been studying extracts from tropical, specially Amazon, plants, to search for new sensitizers for photodynamic therapy of cancer and infectious diseases. Tectona grandis is a genus of tropical hardwood trees in the mint family, Lamiaceae. That is native to south and southeast Asia, but since the end of the 20th century is also gaining ground in the Amazon. The present work aims to evaluate the photodynamic potential of hydro-alcoholic extract from Tectona grandis LF leaves (TGE) and the same extract prepared as the oil-water nanoemulsion (TGE-NE) against melanoma B16 F10 cells. The method for preparation of a stable nanoemulsion with ~20nm particles associated to the TGE (TGE-NE) was successfully developed. We have shown that both free and nanostructured presentations possess the ability to sensitize B16 F10 cells to red light of the LED in vitro. Photodynamic effect was observed for both TGE and TGE-NE because toxicity increased under illumination with red light. While TGE was highly toxic towards melanoma cells under illumination with red light of the LED, it also possessed significant dark toxicity towards both B16 F10 and murine fibroblast NIH3T3 cells. The TGE-NE showed reasonable photocytotoxicity and was much less toxic towards normal cells in the dark compared to free TGE. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Phenothiazinium dyes in association with diode red laser against B16F10 melanoma cells: in vitro study

    Science.gov (United States)

    Miranda, Anderson F.; Santos, Gustavo M. P.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Sampaio, Fernando J. P.; Gomes Júnior, Rafael Araújo; Brugnera, Aldo; Gesteira, Maria F. M.; Zanin, Fátima A. A.; Pinheiro, Antônio Luiz B.; Vannier-Santos, Marcos A.

    2014-02-01

    In Brazil solar incidence is high and continuous throughout the year. Body exposure to sunlight may be a key point in the rates of individuals affected by melanoma and other types of skin cancer in many countries. Brazil already occupies the 15th place in the ranking of melanoma cases and the limitations presented by drugs used in the therapy of this cancer, new approaches are being used in an attempt to decrease the mortality of this malignancy. The aim of this study was to evaluate the effects of phenothiazinium dyes (PD) associated with laser light on murine melanoma (B16F10) in vitro by measuring cell growth using colorimetric assay before and after photodynamic therapy. We used a diode laser (λ660nm, 2.4 J/cm2, 40 mW, 60 s, CW) associated with PD at 12.5 μg/mL, time pre-irradiation of 30 minutes). The following groups were tested: control (LF-), PD (L-F+), Laser (L+F-), Laser + PD (L+F+). The results showed a significant reduction in cell growth in the group treated by the photodynamic therapy compared to the control at 24 and 48 h (p < 0.001). Were showing at 30 min PD has a dose-dependent response on B16F10 cells, but at 24 h did not demonstrated this response.

  19. Reduced paxillin expression contributes to the antimetastatic effect of 4-hydroxycoumarin on B16-F10 melanoma cells

    Directory of Open Access Journals (Sweden)

    Mandoki Juan J

    2008-05-01

    Full Text Available Abstract Background 4-Hydroxycoumarin (4-HC is a coumarin that lacks anticoagulant activity. 4-HC affects the cytoskeletal stability and decreases cell adhesion and motility of the melanoma cell line B16-F10. Together with integrins and other cytoskeletal proteins, paxillin participates in the regulation of cell adhesion and motility, acting as an adapter protein at focal adhesions. The present study determined the participation of paxillin in the reported effects of 4-HC and analyzed the role of paxillin in the formation of melanoma metastases. Results 4-HC decreased protein and mRNA levels of α- and β-paxillin isoforms in B16-F10 cells. Paxillin downregulation correlated with an inadequate translocation of paxillin to focal adhesions and a reduced phosphotyr118-paxillin pool. Consequently, 4-HC altered paxillin-mediated signaling, decreasing the phosphorylation of FAK and the level of GTP-bound Rac-1. These results partially explain the mechanism of the previously reported effects of 4-HC. Additionally, we studied the effect of 4-HC on metastatic potential of B16-F10 cells through experimental metastasis assays. In vitro treatment of cells with 4-HC inhibited their capability to originate pulmonary metastases. 4-HC did not affect cell proliferation or survival, demonstrating that its antimetastatic effect is unrelated to changes on cell viability. We also studied the importance of paxillin in metastasis by transfecting melanoma cells with paxillin-siRNA. Transfection produced a modest reduction on metastatic potential, indicating that: i paxillin plays a role as inducer of melanoma metastasis; and ii paxillin downregulation is not sufficient to explain the antimetastatic effect of 4-HC. Therefore, we evaluated other changes in gene expression by differential display RT-PCR analysis. Treatment with 4-HC produced a downregulation of Adhesion Regulating Molecule-1 (ARM-1, which correlated with a decreased adhesion of melanoma cells to lung

  20. Calreticulin Fragment 39-272 Promotes B16 Melanoma Malignancy through Myeloid-Derived Suppressor Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Xiao-Yan He

    2017-10-01

    Full Text Available Calreticulin (CRT, a multifunctional Ca2+-binding glycoprotein mainly located in the endoplasmic reticulum, is a tumor-associated antigen that has been shown to play protective roles in angiogenesis suppression and anti-tumor immunity. We previously reported that soluble CRT (sCRT was functionally similar to heat shock proteins or damage-associated molecular patterns in terms of ability to activate myeloid cells and elicit strong inflammatory cytokine production. In the present study, B16 melanoma cell lines expressing recombinant CRT fragment 39-272 (sCRT/39-272 in secreted form (B16-CRT, or recombinant enhanced green fluorescence protein (rEGFP (B16-EGFP, were constructed for investigation on the roles of sCRT in tumor development. When s.c. inoculated into C57BL/6 mice, the B16-CRT cells were significantly more aggressive (in terms of solid tumor growth rate than B16-EGFP controls in a TLR4- and myeloid-derived suppressor cells (MDSC-dependent manner. The B16-CRT-bearing mice showed increased Gr1+ MDSC infiltration in tumor tissues, accelerated proliferation of CD11b+Ly6G+Ly6Clow (G-MDSC precursors in bone marrow, and higher percentages of G-MDSCs in spleen and blood, which was mirrored by decreased percentage of dendritic cells (DC in periphery. In in vitro studies, recombinant sCRT/39-272 was able to promote migration and survival of tumor-derived MDSCs via interaction with TLR4, inhibit MDSC differentiation into DC, and also elicit expression of inflammatory proteins S100A8 and S100A9 which are essential for functional maturation and chemotactic migration of MDSCs. Our data provide solid evidence for CRT as a double-edged sword in tumor development.

  1. Data on melanin production in B16F1 melanoma cells in the presence of emu oil

    Directory of Open Access Journals (Sweden)

    Minoru Ito

    2016-12-01

    Full Text Available Here, we present data on the effects of emu oil, obtained from emu (Dromaius novaehollandiae fat deposits, on melanogenesis in B16F1 murine melanoma cells. The cells were cultured in media containing different concentrations of emu oil, and the melanin content of these cells was measured using a microplate reader. Next, melanin content was measured for cells cultured with α-melanocyte-stimulating hormone. This article reports the different melanin contents as μg melanin/mg cellular protein, by using bar graphs with error bars. The present data imply that emu oil reduces the cellular melanin production.

  2. Dual Role of Host Par2 in a Murine Model of Spontaneous Metastatic B16 Melanoma

    Czech Academy of Sciences Publication Activity Database

    Olejár, Tomáš; Větvička, D.; Zadinová, M.; Poučková, P.; Kukal, J.; Ježek, Petr; Matěj, R.

    2014-01-01

    Roč. 34, č. 7 (2014), s. 3511-3515 ISSN 0250-7005 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : PAR2 * melanoma * metastasis * murine model Subject RIV: EA - Cell Biology Impact factor: 1.826, year: 2014

  3. Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

    Czech Academy of Sciences Publication Activity Database

    Caisová, V.; Vieru, A.; Kumžáková, Z.; Glaserová, S.; Husniková, H.; Vácová, N.; Krejčová, G.; Paďouková, L.; Jochmanová, I.; Wolf, K. I.; Chmelař, J.; Kopecký, Jan; Ženka, J.

    2016-01-01

    Roč. 16, č. 1 (2016), č. článku 940. ISSN 1471-2407 Institutional support: RVO:60077344 Keywords : cancer immunotherapy * innate immunity * melanoma * neutrophils * resiquimod * mannan * phagocytosis Subject RIV: EC - Immunology Impact factor: 3.288, year: 2016

  4. Quantification of B16 Melanoma Cells in Lungs Using Triplex Q-PCR - A New Approach to Evaluate Melanoma Cell Metastasis and Tumor Control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Pedersen, Sara R; Lindkvist, Annika

    2014-01-01

    of survival once the tumor has metastasized. In the present study, we have developed a new assay for quantitative analysis of B16 melanoma metastasis in the lungs. We have used a triplex Q-PCR to determine the expression of the melanoma genes GP100/Pmel and tyrosinase-related protein 2 (TRP-2), and found...... the outgrowth of subcutaneous melanomas. Results obtained using Q-PCR were compared to conventional counting of metastatic foci under a dissection microscope. A marked reduction in gene expression was observed in the lungs after vaccination with both vectors; however, Ad-Ii-GP showed the highest protection......, and matching results were obtained by enumeration of visible tumor nodules on the lung surfaces. Finally, we could show that inhibition of tumor metastasis required antigen-specific CD8 T cells and IFNγ, but not perforin. In conclusion, the presented results validate triplex Q-PCR as a fast, objective...

  5. Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315.

    Science.gov (United States)

    Camilio, Ketil André; Berge, Gerd; Ravuri, Chandra Sekhar; Rekdal, Oystein; Sveinbjørnsson, Baldur

    2014-06-01

    Malignant melanoma is the most aggressive and deadliest form of skin cancer due to its highly metastatic potential, which calls for new and improved therapies. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line of defense against pathogens, and several CAPs have shown promising potential as novel anticancer agents. Structure-activity relationship studies on the CAP bovine lactoferricin allowed us to de novo design short chemically modified lytic anticancer peptides. In the present study, we investigated the in vivo antitumor effects of LTX-315 against intradermally established B16 melanomas in syngeneic mice. Intratumoral administration of LTX-315 resulted in tumor necrosis and the infiltration of immune cells into the tumor parenchyma followed by complete regression of the tumor in the majority of the animals. LTX-315 induced the release of danger-associated molecular pattern molecules such as the high mobility group box-1 protein in vitro and the subsequent upregulation of proinflammatory cytokines such as interleukin (IL) 1β, IL6 and IL18 in vivo. Animals cured by LTX-315 treatment were protected against a re-challenge with live B16 tumor cells both intradermally and intravenously. Together, our data indicate that intratumoral treatment with LTX-315 can provide local tumor control followed by protective immune responses and has potential as a new immunotherapeutic agent.

  6. Extracellular acidification by lactic acid suppresses glucose deprivation-induced cell death and autophagy in B16 melanoma cells.

    Science.gov (United States)

    Matsuo, Taisuke; Sadzuka, Yasuyuki

    2018-02-19

    In solid tumors, cancer cells survive and proliferate under conditions of microenvironment stress such as poor nutrients and hypoxia due to inadequate vascularization. These stress conditions in turn activate autophagy, which is important for cancer cell survival. However, autophagy has a contrary effect of inducing cell death in cancer cells cultured in vitro under conditions of glucose deprivation. In this study, we hypothesized that supplementation of lactic acid serves as a means of cell survival under glucose-deprived conditions. At neutral pH, cell death of B16 murine melanoma cells by autophagy under glucose-deprived conditions was observed. However, supplementation of lactic acid suppressed cell death and autophagy in B16 melanoma cells when cultured in glucose-deprived conditions. Sodium lactate, which does not change extracellular pH, did not inhibit cell death, while HCl-adjusted acidic pH suppressed cell death under glucose-deprived conditions. These results suggested that an acidic pH is crucial for cell survival under glucose-deprived conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. The biochemical characterization, stabilization studies and the antiproliferative effect of bromelain against B16F10 murine melanoma cells.

    Science.gov (United States)

    São Paulo Barretto Miranda, Íngara Keisle; Fontes Suzart Miranda, Anderson; Souza, Fernanda Vidigal Duarte; Vannier-Santos, Marcos André; Pirovani, Carlos Priminho; Pepe, Iuri Muniz; Rodowanski, Ivanoé João; Ferreira, Katiúcia Tícila de Souza Eduvirgens; Mendes Souza Vaz, Luciano; de Assis, Sandra Aparecida

    2017-06-01

    The current study aims to extract bromelain from different parts (stem, crown, peels, pulp and leaves) of Ananas comosus var. comosus AGB 772; to determine of optimum pH and temperature; to test bromelain stability in disodium EDTA and sodium benzoate, and to investigate its pharmacological activity on B16F10 murine melanoma cells in vitro. The highest enzymatic activity was found in bromelain extracted from the pulp and peel. The optimum bromelain pH among all studied pineapple parts was 6.0. The optimum temperature was above 50 °C in all bromelain extracts. The fluorescence analysis confirmed the stability of bromelain in the presence of EDTA and sodium benzoate. Bromelain was pharmacologically active against B16F10 melanoma cells and it was possible verifying approximately 100% inhibition of tumor cell proliferation in vitro. Since bromelain activity was found in different parts of pineapple plants, pineapple residues from the food industry may be used for bromelain extraction.

  8. Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways.

    Directory of Open Access Journals (Sweden)

    Kai Zhao

    Full Text Available The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of wogonin. Our date showed that wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by wogonin might be elucidated.

  9. Melanogenesis inhibitory activity of Korean Undaria pinnatifida in mouse B16 melanoma cells

    Directory of Open Access Journals (Sweden)

    Kim Min-Jin

    2014-06-01

    Full Text Available A number of seaweed species are used as traditional foods and medicine in different parts of the world, including Asian countries. However, very few data on the anti-melanogenic effect of seaweed have been published. Undaria pinnatifida (Dolmiyeok, a brown alga, is a traditional food in Jeju Island, the southern regions of the Korea peninsula. In this study, ethylacetate extracts of U. pinnatifida (UPE were examined for their anti-melanogenic potentials. Our results supports the finding that UPE down-regulated melanin content in a dose-dependent pattern. To clarify the target of UPE action in melanogenesis, we performed Western blotting for tyrosinase and microphthalmia-associated transcription factor (MITF, which are key melanogenic enzymes. UPE inhibited tyrosinase and MITF expressions in a dose-dependent manner. These results indicate that treatment with UPE significantly inhibits the melanogenesis in B16 cells, and may be effective in the whitening agent for the skin

  10. Inhibition of metastatic potential of B16-F10 melanoma cell line in vivo and in vitro by biflorin.

    Science.gov (United States)

    Andrade Carvalho, Adriana; da Costa, Patrícia Marçal; Da Silva Souza, Luciana Gregório; Lemos, Telma Leda G; Alves, Ana Paula Negreiros Nunes; Pessoa, Cláudia; de Moraes, Manoel Odorico

    2013-08-14

    The aim of this study was to determine the antimetastatic potential of biflorin using in vivo and in vitro approaches. Biflorin was isolated from Capraria biflora collected in Fortaleza, Ceará, Brazil. Adhesion, migration and invasion assays were performed to avail of the antimetastatic potential of this quinone. Experimental metastasis was performed to avail of the antimetastatic potential of bilflorin using in vivo assay. Treatment with biflorin (25 and 50mg/kg/day) was shown to be effective in reducing B16-F10 melanoma metastasis in C57BL/6 mice. The administration of biflorin at 25mg/kg/day intraperitoneally inhibited the formation of metastases by about 57% compared to untreated control animals. When the animals were treated with 50mg/kg/day intraperitoneally, there was a 71% decrease in the number of lung metastases. Morphological assays showed the presence of hemosiderin and erythrocytes in the lung parenchyma, indicating the occurrence of hemorrhage, probably a side effect of biflorin. Biflorin at non-toxic concentrations (0.5, 1.0 and 1.5g/mL) was tested directly on B16-F10 cells in vitro, and it inhibited cell adhesion to type I collagen and cell motility using the wound-healing assay. These data suggest that biflorin has a promising antimetastatic potential, as shown by its anti-adhesion, anti-migration and anti-invasion properties against a metastatic melanoma cell line. However, further studies are essential to elucidate its mechanism of action. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. The potent pro-oxidant activity of rhododendrol-eumelanin induces cysteine depletion in B16 melanoma cells.

    Science.gov (United States)

    Ito, Shosuke; Okura, Masae; Wakamatsu, Kazumasa; Yamashita, Toshiharu

    2017-01-01

    RS-4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, is known to induce leukoderma in some people. To explore the mechanism underlying this effect, we previously showed that the oxidation of RD with mushroom or human tyrosinase produces cytotoxic quinone oxidation products. We then examined the metabolism of RD in B16F1 melanoma cells in vitro and detected RD-pheomelanin and RD-quinone bound to non-protein and protein thiols. In this study, we examined the changes in glutathione (GSH) and cysteine in B16 cells exposed to RD for up to 24 h. We find that the levels of cysteine, but not those of GSH, decrease during 0.5- to 3-h exposure, due to oxidation to cystine. This pro-oxidant activity was then examined using synthetic melanins. Indeed, we find that RD-eumelanin exerts a pro-oxidant activity as potent as Dopa-pheomelanin. GSH, cysteine, ascorbic acid, and NADH were oxidized by RD-eumelanin with a concomitant production of H 2 O 2 . We propose that RD-eumelanin induces cytotoxicity through its potent pro-oxidant activity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells.

    Science.gov (United States)

    Choo, Soo-Jin; Ryoo, In-Ja; Kim, Kwan Chul; Na, Minkyun; Jang, Jae-Hyuk; Ahn, Jong Seog; Yoo, Ick-Dong

    2014-05-01

    During the course of screens to identify anti-melanogenic agents from natural resources, we found that the methanol extract of the dried flower of Inula britannica L. inhibited melanin synthesis in cultured melanoma cells stimulated with 3-isobutyl-1-methylxanthine (IBMX). A bioassay-guided isolation of the chloroform fraction of the I. britannica using an in vitro melanogenesis inhibition assay led to the isolation of sesquiterpenes, 1-O-acetylbritannilactone (1), britannilactone (2) and neobritannilactone B (3). Compounds 1 and 2 significantly reduced melanin production in a dose-dependent manner with IC50 values of 13.3 and 15.5 μM, respectively, whereas compound 3 was found to be cytotoxic. Compound 1 also inhibited the tyrosinase activity only in cell based-systems. Western blot analysis indicated that compound 1 inhibited melanogenesis by activating extracellular signal-regulated kinase (ERK) and Akt signaling and also inhibiting cAMP related binding protein, which regulates its downstream pathway, including tyrosinase, tyrosinase related protein-1 and TRP-2. These results demonstrated that compound 1, a major sesquiterpene from the flowers of I. britannica, exhibited anti-melanogenic activity by suppression of tyrosinase expression via ERK and Akt signaling. Taken together, our results suggest that these compounds may act as potent natural skin-lightening agents.

  13. Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma-bearing mice under doxorubicin treatment is not connected with their ROS scavenging potential.

    Science.gov (United States)

    Panchuk, Rostyslav R; Skorokhyd, Nadia R; Kozak, Yuliya S; Lehka, Liliya V; Moiseenok, Andrey G; Stoika, Rostyslav S

    2017-04-14

    To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears. Changes in ROS content in B16 melanoma cells under Dx, SeMet, and D-Pt action in vitro were measured by incubation with fluorescent dyes dihydrodichlorofluoresceindiacetate (DCFDA, H2O2-specific) and dihydroethidium (DHE, O2--specific), and further analysis at FL1 (DCFDA) or FL2 channels (DHE) of FACScan flow cytometer. The impact of aforementioned compounds on functional status of mitochondria was measured by Rhodamine 123 assay and further analysis at FL1 channel of FACScan flow cytometer. Selenomethionine (1200 µg/kg) and D-pantethine (500 mg/kg) in combination with Dx (10 mg/kg) significantly reduced tumor-induced neutrophilia, lymphocytopenia, and leukocytosis in comparison to Dx treatment alone. Moreover, SeMet and D-Pt decreased several side effects of Dx, namely an elevated creatinine level in blood and monocytosis, thus normalizing health conditions of B16 melanoma-bearing animals. Our results showed that antioxidants selenomethionine and D-pantethine possess significant nephroprotective and myeloprotective activity toward Dx action on murine B16 melanoma in vivo, but fail to boost a survival of B16 melanoma-bearing animals. The observed cytoprotective effects of studied antioxidants are not directly connected with their ROS scavenging.

  14. Improving anticancer efficacy of (--epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

    Directory of Open Access Journals (Sweden)

    Chen CC

    2014-05-01

    Full Text Available Cheng-Cheung Chen,1,2 Dar-Shih Hsieh,1,3 Kao-Jean Huang,4 Yi-Lin Chan,5 Po-Da Hong,6 Ming-Kung Yeh,6–8,* Chang-Jer Wu1,*1Department of Food Science, National Taiwan Ocean University, Keelung, 2Institute of Preventive Medicine, National Defense Medical Center, Taipei, 3Division of Urology, Department of Surgery, Ren-Ai Hospital, Shulin, New Taipei City, 4Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 5Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 6Materials Technology Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 7School of Pharmacy, National Defense Medical Center, Taipei, 8Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, Republic of China*These authors contributed equally to this workAbstract: (--Epigallocatechin-3-gallate (EGCG, the major bioactive constituent in green tea, has been reported to effectively inhibit the formation and development of tumors. To maximize the effectiveness of EGCG, we attached it to nanogold particles (EGCG-pNG in various ratios to examine in vitro cytotoxicity and in vivo anti-cancer activity. EGCG-pNG showed improved anti-cancer efficacy in B16F10 murine melanoma cells; the cytotoxic effect in the melanoma cells treated with EGCG-pNG was 4.91 times higher than those treated with EGCG. The enhancement is achieved through mitochondrial pathway-mediated apoptosis as determined by annexin V assay, JC-10 staining, and caspase-3, -8, -9 activity assay. Moreover, EGCG-pNG was 1.66 times more potent than EGCG for inhibition of tumor growth in a murine melanoma model. In the hemolysis assay, the pNG surface conjugated with EGCG is most likely the key factor that contributes to the decreased release of hemoglobin from human red blood cells.Keywords: gold nanoparticles, EGCG, anticancer, melanoma

  15. Cohabitation with a B16F10 melanoma-bearer cage mate influences behavior and dendritic cell phenotype in mice.

    Science.gov (United States)

    Tomiyoshi, M Y; Sakai, M; Baleeiro, R B; Stankevicius, D; Massoco, C O; Palermo-Neto, J; Barbuto, J A M

    2009-05-01

    This study evaluated the effects of cohabitation with a B16F10 melanoma-bearer cage mate on behavior and immune functions in mice. Five different experiments were conducted. In each of them, the female mice were divided into two groups: control and experimental. One mouse of each control pair was kept undisturbed and called "companion of health partner" (CHP). One mouse of each experimental pair was inoculated with B16F10 cells and the other, the subject of this study, was called "companion sick partner" (CSP). On Day 20 of cohabitation, behavior and immune parameters from CHP and CSP mice were analyzed. In comparison to the CHP, the CSP mice: (1) presented an increased general locomotion in the open field and a decreased exploration time and number of entries in the plus-maze open arms; (2) had an enhanced expression of the CD80 costimulatory molecule on Iab(+)CD11c(+) spleen cells, but no differences were found on lymph nodes cells; (3) presented an altered differentiation of bone marrow cells in the presence of GM-CSF, IL-4, and LPS in vitro, resulting in a lower percentage of Iab(+)CD80(+) cells; (4) had a deficit in the establishment of a Delayed Type of Hypersensitivity to ovalbumin, which was associated to an in vitro proliferation of an IL-10-producing lymphocyte subpopulation after ovalbumin stimulation. Corticosterone levels detected on Day 20 of cohabitation were similar in CHP and CSP mice. It is shown here that DCs phenotype in mice is affected by conditions associated with behavioral alterations indicative of an anxiety-like state induced by the cohabitation with a tumor-bearer conspecific. This phenomenon occurred probably through a nondependent corticosterone mechanism.

  16. A novel bioactive chalcone of Morus australis inhibits tyrosinase activity and melanin biosynthesis in B16 melanoma cells.

    Science.gov (United States)

    Takahashi, Makoto; Takara, Kensaku; Toyozato, Tomonao; Wada, Koji

    2012-01-01

    The methanol extract of Morus australis (shimaguwa) acts as a whitening agent due to the inhibition of tyrosinase activity. In order to explore the mechanism(s) of the whitening action, constituents of the 95% methanol extract from the dried stems of shimaguwa were isolated and their skin-whitening capacity was examined. Bioassay-guided fractionation of the methanol soluble extract of shimaguwa led to the isolation of 2, 4, 2', 4'-hydroxycalcone (chalcone 1) and three analogues of chalcone 1 with 3'-substituted resorcinol moieties (chalcones 2-4). Chalcone derivative 4 proved to be a novel compound and was fully characterized. Chalcones 1-4 were evaluated for inhibition activity on mushroom tyrosinase using L-tyrosine as the substrate. The parent chalcone 1 was a highly effective inhibitor of tyrosinase activity (IC₅₀ = 0.21 μM) compared to arbutin (IC₅₀ = 164 μM). Compared to chalcone 1, chalcones 2 and 3, which possess 3'-substituted isoprenyl or bulky 2-benzoylbiphenyl, showed significantly decreased tyrosinase activity, while chalcone 4, possessing 3'-substituted 2-hydroxy-1-pentene group, showed slightly increased activity.The effects of chalcones 1-4 on melanin synthesis, without affecting cell growth, were assayed in melanin-producing B16 murine melanoma cells. Chalcone 3 significantly reduced cell viability before reaching the IC₅₀ value for melanin synthesis. In contrast, the inhibitory effects of chalcones 1, 2 and 4 were more than 100-fold greater than that of arbutin, with little or no cytotoxicity. More significantly, chalcone 2, which exhibited less tyrosinase inhibitory activity compared to the parent chalcone 1, showed the highest inhibition of melanin synthesis in B16 cells among the chalcones tested. Accordingly, chalcones 1 and 2, and the novel chalcone 4 might be the active components responsible for the whitening ability of shimaguwa. Moreover, whitening ability was not exclusively due to tyrosinase inhibition.

  17. The use of Zymosan A and bacteria anchored to tumor cells for effective cancer immunotherapy: B16-F10 murine melanoma model

    Czech Academy of Sciences Publication Activity Database

    Waldmannová, E.; Caisová, V.; Fáberová, J.; Sváčková, P.; Kovářová, M.; Sváčková, D.; Kumžáková, Z.; Jačková, A.; Vácová, N.; Nedbalová, P.; Horká, Marie; Kopecký, Jan; Ženka, J.

    2016-01-01

    Roč. 39, OCT (2016), s. 295-306 ISSN 1567-5769 Institutional support: RVO:68081715 ; RVO:60077344 Keywords : melanoma B16-F10, * cancer immunotherapy * frustrated phagocytosis Subject RIV: CB - Analytical Chemistry, Separation; EC - Immunology (BC-A) Impact factor: 2.956, year: 2016

  18. Proteomic analyses for profiling regulated proteins/enzymes by Fucus vesiculosus fucoidan in B16 melanoma cells: A combination of enzyme kinetics functional study.

    Science.gov (United States)

    Wang, Zhi-Jiang; Zheng, Li; Yang, Jun-Mo; Kang, Yani; Park, Yong-Doo

    2018-06-01

    Fucoidans are complex sulfated polysaccharides that have a wide range of biological activities. Previously, we reported the various effects of Fucus vesiculosus fucoidan on tyrosinase and B16 melanoma cells. In this study, to identify fucoidan-targeted proteins in B16 melanoma cells, we performed a proteomics study and integrated enzyme kinetics. We detected 19 candidate proteins dysregulated by fucoidan treatment. Among the probed proteins, the enzyme kinetics of two candidate enzymes, namely lactate dehydrogenase (LDH) as an upregulated protein and superoxide dismutase (SOD) as a downregulated enzyme, were determined. The enzyme kinetics results showed that Fucus vesiculosus fucoidan significantly inhibited LDH catalytic function while it did not affect SOD activity even at a high dose, while only slightly decreased activity (up to 10%) at a low dose. Based on our previous and present observations, fucoidan could inhibit B16 melanoma cells growth via regulating proteins/enzymes expression levels such as LDH and SOD known as cell survival biomarkers. Interestingly, both expression level and enzyme catalytic activity of LDH were regulated by fucoidan, which could directly induce the apoptotic effect on B16 melanoma cells along with SOD downregulation. This study highlights how combining proteomics with enzyme kinetics can yield valuable insights into fucoidan targets. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Synthesis and characterization of copper nanoparticles stabilized with Quisqualis indica extract: Evaluation of its cytotoxicity and apoptosis in B16F10 melanoma cells.

    Science.gov (United States)

    Mukhopadhyay, Ria; Kazi, Julekha; Debnath, Mita Chatterjee

    2018-01-01

    Green synthesis of metallic nanoparticles is a cost-effective environment-friendly technique and Quisqualis indica has ethnomedicinal values. With this background in this study, the floral extract of Q. indica was used to fabricate copper nanoparticles (QCuNPs) from copper acetate. Biophysical analysis revealed the formation of spherical, monodisperse, crystalline QCuNPs. Significant cytotoxic potentials of the nanoformulation were determined by MTT and lactate dehydrogenase (LDH) assay on B16F10 melanoma cells. Estimation of GSH and ROS demonstrated that QCuNPs induced melanoma cell death by induction of oxidative stress. Gene transcript analysis showed up-regulation of caspase-dependent as well as caspase-independent (AIF) apoptotic genes in treated cells. Comparative proteomics study mostly showed the abundance of apoptotic and cell cycle arrest proteins in treated samples. The in vivo therapeutic efficacy was studied in mice bearing B16F10 melanoma tumor where a significant decrease in tumor growth was observed in nanoparticles treated animal model. In conclusion, QCuNPs caused cytotoxicity and apoptosis in melanoma cells and its mechanism was established from gene expression and proteomic studies. QCuNPs exhibited potential suppression of B16F10 melanoma cell proliferation and substantial inhibition of tumor growth in animals. As per our information, this is the first study exploring the potential of Q. indica for the formulation of eco-friendly copper nanoparticle which will have great future application in the medicinal field. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Compounds isolated from the aerial part of Crataegus azarolus inhibit growth of B16F10 melanoma cells and exert a potent inhibition of the melanin synthesis.

    Science.gov (United States)

    Mustapha, Nadia; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2015-02-01

    Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study, we have investigated inhibitory capacity of vitexin-2''-O-rhamnoside as well as the extract from which it was isolated, i.e. the ethyl acetate extract obtained from the leaves of Crataegus azarolus, on mouse melanoma (B16F10) proliferation. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475nm. Ethyl acetate extract and vitexin-2''-O-rhamnoside exhibited significant anti-proliferative activity against B16F10 melanoma cells after incubation for 48hours with IC50s of 50μg/mL and 20μM, respectively. Furthermore, these two compounds have the ability to reduce the melanin content by inhibiting the tyrosinase activity of B16F10 cells. Thus, further investigations are merited to ascertain their potential application in treating hyperpigmentation disorders. Copyright © 2014. Published by Elsevier Masson SAS.

  1. Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells.

    Science.gov (United States)

    Bunea, Andrea; Rugină, Dumitriţa; Sconţa, Zoriţa; Pop, Raluca M; Pintea, Adela; Socaciu, Carmen; Tăbăran, Flaviu; Grootaert, Charlotte; Struijs, Karin; VanCamp, John

    2013-11-01

    Blueberry consumption is associated with health benefits contributing to a reduced risk for cardiovascular disease, diabetes and cancer. The aim of this study was to determine the anthocyanin profile of blueberry extracts and to evaluate their effects on B16-F10 metastatic melanoma murine cells. Seven blueberry cultivars cultivated in Romania were used. The blueberry extracts were purified over an Amberlite XAD-7 resin and a Sephadex LH-20 column, in order to obtain the anthocyanin rich fractions (ARF). The antioxidant activity of the ARF of all cultivars was evaluated by ABTS, CUPRAC and ORAC assays. High performance liquid chromatography followed by electrospray ionization mass spectrometry (HPLC-ESI-MS) was used to identify and quantify individual anthocyanins. The anthocyanin content of tested cultivars ranged from 101.88 to 195.01 mg malvidin-3-glucoside/100g fresh weight. The anthocyanin rich-fraction obtained from cultivar Torro (ARF-T) was shown to have the highest anthocyanin content and antioxidant activity, and inhibited B16-F10 melanoma murine cells proliferation at concentrations higher than 500 μg/ml. In addition, ARF-T stimulated apoptosis and increased total LDH activity in metastatic B16-F10 melanoma murine cells. These results indicate that the anthocyanins from blueberry cultivar could be used as a chemopreventive or adjuvant treatment for metastasis control. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Ethanol extract of Lycoris radiata induces cell death in B16F10 melanoma via p38-mediated AP-1 activation.

    Science.gov (United States)

    Son, Minsik; Kim, Aeyung; Lee, Jaewoo; Park, Chul-Hong; Heo, Jin-Chul; Lee, Hyun-Jin; Lee, Sang-Han

    2010-08-01

    Some active alkaloids isolated from Lycoris, a bulbous perennial herb, was shown to possess various anti-tumor and anti-inflammatory activities. In this study, we evaluated the in vitro apoptotic effect of ethanol extract from Lycoris radiata (LRE) and further probed the underlying molecular mechanisms of LRE effects. The survival rate of B16F10 melanoma cells exposed to LRE was decreased in a dose-dependent manner, cell growth was retarded by arresting cell cycle at G1 phase and apoptotic appearance such as caspase-3 activation as well as DNA fragmentation was observed by LRE treatment. In addition, LRE induced p38 and c-Jun phosphorylation, followed by activation of transcription factor AP-1. Pretreatment with the p38 inhibitor (SB203580) blocked LRE-induced AP-1 transcriptional activity, and curcumin, AP-1 inhibitor, dramatically inhibited LRE-induced apoptosis in B16F10 melanoma cells. Our results collectively indicate that LRE-mediated apoptosis occurs through the activation of p38 and AP-1 pathway and potentially LRE exhibits anti-cancer activity against B16F10 melanoma cells.

  3. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali

    2012-01-01

    Full Text Available The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group.

  4. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    International Nuclear Information System (INIS)

    Ali, F. R.; Lear, J. T.

    2012-01-01

    The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group

  5. Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration

    Directory of Open Access Journals (Sweden)

    So Young Park

    2014-07-01

    Full Text Available Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP-9, tissue inhibitor of metalloproteinase (TIMP-1, urokinase plasminogen activator (uPA, and vascular cell adhesion molecule (VCAM-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration.

  6. Incidence of melanoma in organ transplant recipients in Alberta, Canada.

    Science.gov (United States)

    Tran, Mimi; Sander, Megan; Ravani, Pietro; Mydlarski, P Régine

    2016-10-01

    Many studies have documented the increased risk of non-melanoma skin cancers in organ transplant recipients (OTRs). However, the incidence of melanoma is less well defined. To date, there have been no studies on the incidence of melanoma in Canadian OTRs. Herein, we determine the incidence and clinical features of melanoma in a cohort of OTRs in Southern Alberta, Canada. We used the Southern Alberta Transplant database to identify kidney and liver transplant recipients between the years 2000 and 2012. This population was cross-referenced with the Alberta Cancer Registry for a diagnosis of melanoma. The clinical features of all cases were obtained, and the standardized incidence rate was calculated. We identified 993 OTR patients, representing 5955 person-years. Only one patient developed a melanoma post-transplant, and this was a nodular melanoma. The age-standardized incidence rate was 11 per 100 000 (0.6 per 5955), compared to 13.4 per 100 000 in the general Alberta population (incidence rate ratio of 1.29, with 95% confidence interval of 0.17 to 9.82). This is the first Canadian study to investigate the association between organ transplantation and melanoma. Our study did not identify an increased risk of developing a de novo melanoma post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Casticin impairs cell migration and invasion of mouse melanoma B16F10 cells via PI3K/AKT and NF-κB signaling pathways.

    Science.gov (United States)

    Shih, Yung-Luen; Chou, Hsiao-Min; Chou, Hsiu-Chen; Lu, Hsu-Feng; Chu, Yung-Lin; Shang, Hung-Sheng; Chung, Jing-Gung

    2017-09-01

    Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners. Casticin affected cell migration and invasion in B16F10 cells were examined by wound healing mobility assay and Boyden chamber migration and invasion assay and results indicated that casticin inhibited cell migration and invasion in dose-dependent manners. Western blotting was used to examine the protein expression of B16F10 cells after exposed to casticin and the results showed that casticin decreased the expressions of MMP-9, MMP-2, MMP-1, FAK, 14-3-3, GRB2, Akt, NF-κB p65, SOS-1, p-EGFR, p-JNK 1/2, uPA, and Rho A in B16F10 cells. Furthermore, cDNA microarray assay was used to show that casticin affected associated gene expression of cell migration and invasion and the results indicated that casticin affected some of the gene expression such as increased SCN1B (cell adhesion molecule 1) and TIMP2 (TIMP metallopeptidase inhibitor 2) and decreased NDUFS4 (NADH dehydrogenase (ubiquinone) Fe-S protein4), VEGFA (vascular endothelial growth factor A), and DDIT3 (DNA-damage-inducible transcript 3) which associated cell migration and invasion in B16F10 cells. Based on those observations, we suggest that casticin could be used as a novel anticancer metastasis of melanoma cancer in the future. © 2017 Wiley Periodicals, Inc.

  8. Antitumor Effects In Vitro and In Vivo and Mechanisms of Protection against Melanoma B16F10-Nex2 Cells By Fastuosain, a Cysteine Proteinase from Bromelia fastuosa

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    Carla A. Guimarães-Ferreira

    2007-09-01

    Full Text Available In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57BI/6 mice, fastuosain and bromelain injected intraperitoneally were protective, very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, became round and detached, forming strongly bound cell clusters in suspension. Peritoneal cells recruited and activated by fastuosain treatment (mainly monocytic cells and lymphocytes migrated to the lung, where pulmonary melanoma metastases grew. Adoptive transference of peritoneal cells recruited by fastuosain had no protective effect against lung metastases in recipient mice. Treatment of green fluorescent protein -chimeric animals with fastuosain did not change the number of cells that migrated to the lung, compared to PBSinjected control mice, but the number of positive major histocompatibility complex class II cells increased with fastuosain treatment. Murine antibodies against fastuosain, bromelain, cathepsins B and L crossreacted in ELISA and recognized surface and cytoplasmic components expressed on B16F10-Nex2 cells. Anti-fastuosain antibodies were cytotoxic/lytic to B16F10-Nex2 cells. Antitumor effects of fastuosain involve mainly the direct effect of the enzyme and elicitation of protective antibodies.

  9. Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines.

    Science.gov (United States)

    Santhanam, Ramesh Kumar; Ahmad, Syahida; Abas, Faridah; Safinar Ismail, Intan; Rukayadi, Yaya; Tayyab Akhtar, Muhammad; Shaari, Khozirah

    2016-05-24

    Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

  10. Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF Cell Lines

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    Ramesh Kumar Santhanam

    2016-05-01

    Full Text Available Zanthoxylum rhetsa is an aromatic tree, known vernacularly as “Indian Prickly Ash”. It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin, a berberine alkaloid (columbamine and a triterpenoid (lupeol from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF and mouse melanoma (B16-F10 cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

  11. STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body.

    Science.gov (United States)

    Sekine, Yuichi; Togi, Sumihito; Muromoto, Ryuta; Kon, Shigeyuki; Kitai, Yuichi; Yoshimura, Akihiko; Oritani, Kenji; Matsuda, Tadashi

    2015-07-10

    Melanoma is the most serious type of skin cancer, with a highly metastatic phenotype. In this report, we show that signal transducing adaptor protein 2 (STAP-2) is involved in cell migration, proliferation, and melanogenesis as well as chemokine receptor expression and tumorigenesis in B16F10 melanoma cells. This was evident in mice injected with STAP-2 shRNA (shSTAP-2)-expressing B16F10 cells, which infiltrated organs in a completely different pattern from the original cells, showing massive colonization in the liver, kidney, and neck but not in the lung. The most important finding was that STAP-2 expression determined tyrosinase protein content. STAP-2 colocalized with tyrosinase in lysosomes and protected tyrosinase from protein degradation. It is noteworthy that B16F10 cells with knocked down tyrosinase showed similar cell characteristics as shSTAP-2 cells. These results indicated that tyrosinase contributed to some cellular events beyond melanogenesis. Taken together, one possibility is that STAP-2 positively regulates the protein levels of tyrosinase, which determines tumor invasion via controlling chemokine receptor expression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells

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    Maeda, Toyonobu; Suzuki, Atsuko; Koga, Kaori; Miyamoto, Chihiro; Maehata, Yojiro; Ozawa, Shigeyuki; Hata, Ryu-Ichiro; Nagashima, Yoji; Nabeshima, Kazuki; Miyazaki, Kaoru; Kato, Yasumasa

    2017-01-01

    Extracellular acidity is a hallmark of solid tumors and is associated with metastasis in the tumor microenvironment. Acidic extracellular pH (pHe) has been found to increase intracellular Ca2+ and matrix metalloproteinase-9 (MMP-9) expression by activating NF-κB in the mouse B16 melanoma model. The present study assessed whether TRPM5, an intracellular Ca2+-dependent monovalent cation channel, is associated with acidic pHe signaling and induction of MMP-9 expression in this mouse melanoma model. Treatment of B16 cells with Trpm5 siRNA reduced acidic pHe-induced MMP-9 expression. Enforced expression of Trpm5 increased the rate of acidic pHe-induced MMP-9 expression, as well as increasing experimental lung metastasis. This genetic manipulation did not alter the pHe critical for MMP-9 induction but simply amplified the percentage of inducible MMP-9 at each pHe. Treatment of tumor bearing mice with triphenylphosphine oxide (TPPO), an inhibitor of TRPM5, significantly reduced spontaneous lung metastasis. In silico analysis of clinical samples showed that high TRPM5 mRNA expression correlated with poor overall survival rate in patients with melanoma and gastric cancer but not in patients with cancers of the ovary, lung, breast, and rectum. These results showed that TRPM5 amplifies acidic pHe signaling and may be a promising target for preventing metastasis of some types of tumor. PMID:29108231

  13. TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells.

    Science.gov (United States)

    Maeda, Toyonobu; Suzuki, Atsuko; Koga, Kaori; Miyamoto, Chihiro; Maehata, Yojiro; Ozawa, Shigeyuki; Hata, Ryu-Ichiro; Nagashima, Yoji; Nabeshima, Kazuki; Miyazaki, Kaoru; Kato, Yasumasa

    2017-10-03

    Extracellular acidity is a hallmark of solid tumors and is associated with metastasis in the tumor microenvironment. Acidic extracellular pH (pH e ) has been found to increase intracellular Ca 2+ and matrix metalloproteinase-9 (MMP-9) expression by activating NF-κB in the mouse B16 melanoma model. The present study assessed whether TRPM5, an intracellular Ca 2+ -dependent monovalent cation channel, is associated with acidic pH e signaling and induction of MMP-9 expression in this mouse melanoma model. Treatment of B16 cells with Trpm5 siRNA reduced acidic pH e -induced MMP-9 expression. Enforced expression of Trpm5 increased the rate of acidic pH e -induced MMP-9 expression, as well as increasing experimental lung metastasis. This genetic manipulation did not alter the pH e critical for MMP-9 induction but simply amplified the percentage of inducible MMP-9 at each pH e . Treatment of tumor bearing mice with triphenylphosphine oxide (TPPO), an inhibitor of TRPM5, significantly reduced spontaneous lung metastasis. In silico analysis of clinical samples showed that high TRPM5 mRNA expression correlated with poor overall survival rate in patients with melanoma and gastric cancer but not in patients with cancers of the ovary, lung, breast, and rectum. These results showed that TRPM5 amplifies acidic pH e signaling and may be a promising target for preventing metastasis of some types of tumor.

  14. cRGD-installed docetaxel-loaded mertansine prodrug micelles: redox-triggered ratiometric dual drug release and targeted synergistic treatment of B16F10 melanoma

    Science.gov (United States)

    Zhong, Ping; Qiu, Min; Zhang, Jian; Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Zhong, Zhiyuan

    2017-07-01

    Combinatorial chemotherapy, which has emerged as a promising treatment modality for intractable cancers, is challenged by a lack of tumor-targeting, robust and ratiometric dual drug release systems. Here, docetaxel-loaded cRGD peptide-decorated redox-activable micellar mertansine prodrug (DTX-cRGD-MMP) was developed for targeted and synergistic treatment of B16F10 melanoma-bearing C57BL/6 mice. DTX-cRGD-MMP exhibited a small size of ca. 49 nm, high DTX and DM1 loading, low drug leakage under physiological conditions, with rapid release of both DTX and DM1 under a cytoplasmic reductive environment. Notably, MTT and flow cytometry assays showed that DTX-cRGD-MMP brought about a synergistic antitumor effect to B16F10 cancer cells, with a combination index of 0.37 and an IC50 over 3- and 13-fold lower than cRGD-MMP (w/o DTX) and DTX-cRGD-Ms (w/o DM1) controls, respectively. In vivo studies revealed that DTX-cRGD-MMP had a long circulation time and a markedly improved accumulation in the B16F10 tumor compared with the non-targeting DTX-MMP control (9.15 versus 3.13% ID/g at 12 h post-injection). Interestingly, mice treated with DTX-cRGD-MMP showed almost complete growth inhibition of B16F10 melanoma, with tumor inhibition efficacy following an order of DTX-cRGD-MMP > DTX-MMP (w/o cRGD) > cRGD-MMP (w/o DTX) > DTX-cRGD-Ms (w/o DM1) > free DTX. Consequently, DTX-cRGD-MMP significantly improved the survival rates of B16F10 melanoma-bearing mice. Importantly, DTX-cRGD-MMP caused little adverse effects as revealed by mice body weights and histological analyses. The combination of two mitotic inhibitors, DTX and DM1, appears to be an interesting approach for effective cancer therapy.

  15. Spatane diterpinoid from the brown algae, Stoechospermum marginatum induces apoptosis via ROS induced mitochondrial mediated caspase dependent pathway in murine B16F10 melanoma cells.

    Science.gov (United States)

    Velatooru, Loka Reddy; Baggu, Chinna Babu; Janapala, Venkateswara Rao

    2016-12-01

    Spatane diterpinoids isolated from the brown marine algae Stoechospermum marginatum were known to have cytotoxic effects in human cancerous cell lines and murine melanoma cells; the underling apoptotic mechanism of diterpinoids still remains unclear so far. Thus, in the present study, the apoptotic mechanism of a spatane diterpinoid, 5(R), 19-diacetoxy-15,18(R and S), dihydro spata-13, 16(E)-diene (DDSD) was investigated mainly in B16F10 melanoma cells because they were most susceptible to DDSD than THP1, U937, COLO205, and HL60 cells. The treatment of B6F10 cells with DDSD resulted in morphological alterations, nuclear condensation, and DNA fragmentation, which leads to cell growth inhibition in a concentration-dependent manner. Data indicate that DDSD induced the generation of ROS, consequentially caused alteration in Bax/Bcl-2 ratio that disrupted the inner mitochondrial transmembrane potential (ΔΨm) resulting in cytochrome c redistribution to the cytoplasm and activation of caspase-mediated apoptotic pathway. Flow cytometric analysis clearly indicated that the DDSD inducing phosphatidylserine externalization and mediated "S-phase" arrest in cell cycle. In addition, results also found that DDSD induced apoptosis through deregulating PI3K/AKT signaling pathway. The anti-tumor activity of DDSD was evaluated in C57BL/6 mice bearing B16F10 melanoma. It effectively inhibited tumor growth (volume and weight) in a dose dependent manner, yet without apparent toxic effects. Morphology and apoptotic status of tumor tissues in the treated mice were assessed by microscopy and TUNEL assay, respectively. Our study shows a therapeutic potential of DDSD for the treatment of malignant melanoma and a new source of anticancer drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Inhibition of metastasis of B16F-10 melanoma cells in C57BL/6 mice by an extract of Calendula officinalis L flowers.

    Science.gov (United States)

    Preethi, Korangath C; Siveen, Kodappully S; Kuttan, Ramadasan; Kuttan, Girija

    2010-01-01

    To determine the effect of a Calendula officinalis flower extract on lung metastasis by B16F-10 melanoma cells in C57BL/6 mice. Male mice were injected with B16F-10 melanoma cells through the tail vein and simultaneously treated with C.officinalis flower extract. Parameters studied were lung tumor nodule count, life span of animals, gamma glutamyl transpeptidase activity, sialic acid, TNF-α, IL-1β, IL-6, IL-2, GM-CSF, VEGF and TIMP-1 levels in serum, and lung hydroxyproline, uronic acid and hexosamine levels, as well as histopathological features. Effects of C.officinalis on the expression of various genes involved in metastasis like matrix metalloproteases (MMPs), tissue inhibitor of metalloproteases (TIMPs), prolyl hydoxylase, lysyl oxidase, nm23, and proinflammatory cytokines were also investigated. Simultaneous administration of C. officinalis extract to tumor bearing C57BL/6 mice reduced the lung tumor nodules by 74% with 43.3% increase in life span. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-glutamyl transpeptidase in the metastatic controls were found to be significantly lowered in the C. officinalis treated animals. The extract also inhibited expression of MMP-2, MMP-9, prolyl hydroxylase and lysyl oxidase and activated TIMP-1 and TIMP-2 and downregulated proinflammatory cytokines. The present investigation indicated antimetastatic effects of Calendula officinalis flowers through the inhibition of key enzymes involved in processes of metastasis.

  17. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

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    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  18. Melaleuca quinquenervia essential oil inhibits α-melanocyte-stimulating hormone-induced melanin production and oxidative stress in B16 melanoma cells.

    Science.gov (United States)

    Chao, Wen-Wan; Su, Chia-Chi; Peng, Hsin-Yi; Chou, Su-Tze

    2017-10-15

    Essential oils are odorous, volatile products of plant secondary metabolism, which are found in many leaves and stems. They show important biological activities, which account for the development of aromatherapy used in complementary and alternative medicine. The essential oil extracted from Melaleuca quinquenervia (Cav.) S.T. Blake (paperbark) (MQ-EO) has various functional properties. The aim of this study is to investigate the chemical composition of MQ-EO by using gas chromatography-mass spectrometry (GC-MS) and evaluate its tyrosinase inhibitory activity. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics was used to identify 18 components in MQ-EO. The main components identified were 1,8-cineole (21.60%), α-pinene (15.93%), viridiflorol (14.55%), and α-terpineol (13.73%). B16 melanoma cells were treated with α-melanocyte-stimulating hormone (α-MSH) in the presence of various concentrations of MQ-EO or its major compounds. Cell viability was accessed by MTT assay and cellular tyrosinase activity and melanin content were determined by using spectrophotographic methods. The antioxidant mechanism of MQ-EO in α-MSH stimulated B16 cells was also investigated. In α-melanocyte-stimulating hormone (α-MSH)-stimulated murine B16 melanoma cells, MQ-EO, 1,8-cineole, α-pinene, and α-terpineol significantly reduced melanin content and tyrosinase activity. Moreover, MQ-EO, 1,8-cineole, α-pinene, and α-terpineol decreased malondialdehyde (MDA) levels. In addition, restored glutathione (GSH) levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities were increased in α-MSH-stimulated B16 cells. MQ-EO not only decreased apoptosis but also reduced DNA damage in α-MSH stimulated B16 cells. These results showed that MQ-EO and its main components, 1,8-cineole, α-pinene, and α-terpineol, possessed potent anti-tyrosinase and anti-melanogenic activities besides the antioxidant properties. The active functional components of MQ

  19. A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM

    Science.gov (United States)

    Manangon, Eliana; Hood, Joshua L.; Wickline, Samuel A.; Fernandez, Diego P.; Johnson, William P.; Gale, Bruce K.

    2015-01-01

    Exosomes participate in cancer metastasis, but studying them presents unique challenges as a result of their small size and purification difficulties. Asymmetrical field flow fractionation with in-line ultraviolet absorbance, dynamic light scattering, and multi-angle light scattering was applied to the size separation and characterization of non-labeled B16-F10 exosomes from an aggressive mouse melanoma cell culture line. Fractions were collected and further analyzed using batch mode dynamic light scattering, transmission electron microscopy and compared with known size standards. Fractogram peak positions and computed radii show good agreement between samples and across fractions. Ultraviolet absorbance fractograms in combination with transmission electron micrographs were able to resolve subtle heterogeneity of vesicle retention times between separate batches of B16-F10 exosomes collected several weeks apart. Further, asymmetrical field flow fractionation also effectively separated B16-F10 exosomes into vesicle subpopulations by size. Overall, the flow field flow fractionation instrument combined with multiple detectors was able to rapidly characterize and separate exosomes to a degree not previously demonstrated. These approaches have the potential to facilitate a greater understanding of exosome function by subtype, as well as ultimately allow for “label-free” isolation of large scale clinical exosomes for the purpose of developing future exosome-based diagnostics and therapeutics. PMID:25084738

  20. Inhibitory Effects of Adlay Extract on Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Huey-Chun Huang

    2014-09-01

    Full Text Available The aim of this study was to determine the effects of adlay extract on melanin production and the antioxidant characteristics of the extract. The seeds were extracted by the supercritical fluid CO2 extraction (SFE method. The effect of adlay extract on melanin production was evaluated using mushroom tyrosinase activity assay, intracellular tyrosinase activity, antioxidant properties and melanin content. Those assays were performed spectrophotometrically. In addition, the expression of melanogenesis-related proteins was determined by western blotting. The results revealed that the adlay extract suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 cells. The adlay extract decreased the expression of microphthalmia-associated transcription factor (MITF, tyrosinase, tyrosinase related protein-1 (TRP-1 and tyrosinase related protein-2 (TRP-2. The extract also exhibited antioxidant characteristics such as free radical scavenging capacity and reducing power. It effectively decreased intracellular reactive oxygen species (ROS levels in B16F10 cells. We concluded that the adlay extract inhibits melanin production by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2. The antioxidant properties of the extract may also contribute to the inhibition of melanogenesis. The adlay extract can therefore be applied as an inhibitor of melanogenesis and could also act as a natural antioxidant in skin care products.

  1. Inhibitory Effect of Dried Pomegranate Concentration Powder on Melanogenesis in B16F10 Melanoma Cells; Involvement of p38 and PKA Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Su Jin Kang

    2015-10-01

    Full Text Available Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1, TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA, cAMP response element-binding protein (CREB, mitogen-activated protein kinases (MAPKs, phosphatidylinositol 3-kinase (PI3K, serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1 were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.

  2. Inhibitory Effect of Dried Pomegranate Concentration Powder on Melanogenesis in B16F10 Melanoma Cells; Involvement of p38 and PKA Signaling Pathways

    Science.gov (United States)

    Kang, Su Jin; Choi, Beom Rak; Lee, Eun Kyoung; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Lee, Young Joon; Ku, Sae Kwang

    2015-01-01

    Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP) on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1), TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA), cAMP response element-binding protein (CREB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β) were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1) were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP. PMID:26473849

  3. Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice.

    Science.gov (United States)

    Hu, Zhengping; Ye, Liang; Xing, Yingying; Hu, Jinhang; Xi, Tao

    2018-01-09

    The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and αPD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8 + and CD4 + T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor. The combination treatment also produced synergistic increase in P-ERK1/2 level in spleen. Immunohistochemistry shown that SEP induced the PD-L1 expression in melanoma tissue possibly by promoting IFN-γ excretion, which led to the synergistic anti-tumor effects of aPD-L1 and SEP. Furthermore, in the purified T lymphocyte from the naive mice, the combination of SEP and αPD-L1 had more potent than SEP or αPD-L1 in promoting T lymphocyte proliferation and cytokines secretion including IL-2 and IFN-γ, at least partially by activating MEK/ERK pathway. Our study provides the scientific basis for a clinical trial that would involve combination of anti-PD-L1 mAb and SEP for sustained melanoma control.

  4. The Cytolytic Amphipathic β(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma.

    Science.gov (United States)

    Eike, Liv-Marie; Mauseth, Brynjar; Camilio, Ketil André; Rekdal, Øystein; Sveinbjørnsson, Baldur

    2016-01-01

    In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated cells. The use of a murine melanoma model demonstrated that the majority of animals treated with intratumoural injections of LTX-401 showed complete and long-lasting remission. Taken together, these results demonstrate the potential of LTX-401 as an immunotherapeutic agent for the treatment of solid tumors.

  5. Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Myra O. Villareal

    2013-01-01

    Full Text Available Argan (Argania spinosa L. oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decrease in melanin content. Western blot results showed that the expression levels of tyrosinase (TYR, tyrosinase-related protein 1 (TRP1, and dopachrome tautomerase (DCT proteins were decreased. In addition, there was an increase in the activation of MITF and ERK1/2. Real-time PCR results revealed a downregulation of Tyr, Trp1, Dct, and Mitf mRNA expressions. Argan oil treatment causes MITF phosphorylation which subsequently inhibited the transcription of melanogenic enzymes, TYR and DCT. The inhibitory effect of argan oil on melanin biosynthesis may be attributed to tocopherols as well as the synergistic effect of its components. The results of this study provide the scientific basis for the traditionally established benefits of argan oil and present its therapeutic potential against hyperpigmentation disorders.

  6. Whitening and anti-wrinkle activities of ferulic acid isolated from Tetragonia tetragonioides in B16F10 melanoma and CCD-986sk fibroblast cells.

    Science.gov (United States)

    Park, Hye-Jin; Cho, Jun-Hyo; Hong, Shin-Hyub; Kim, Dong-Hee; Jung, Hee-Young; Kang, In-Kyu; Cho, Young-Je

    2018-01-01

    Ferulic acid isolated from Tetragonia tetragonioides was tested for its whitening effect on the B16F10 mouse melanoma cell line and its anti-wrinkle activity on the CCD-986sk human dermal fibroblast cell line. Ferulic acid, one of the primary phenolic compounds that can be isolated from T. tetragonioides, has been reported to show potential as a functional food, for its whitening effect and anti-wrinkle activity. To measure its whitening and anti-wrinkle activities, cells were treated with ferulic acid isolated from T. tetragonioides at concentrations between 5 and 20 μM. Ferulic acid showed no cytotoxicity at concentrations up to 20 μM. Ferulic acid inhibited melanin synthesis, tyrosinase expression, and microphthalmia transcription factor expression in B16F10 cells stimulated with α-melanocyte stimulating hormone. Ferulic acid induced procollagen synthesis, hyaluronic acid synthesis, tissue inhibitor of metalloproteinase synthesis, and inhibited matrix metalloproteinase (MMP)-1 and MMP-9 expression in CCD-986sk cells stimulated with UV-B. On the basis of these results, we conclude that ferulic acid isolated from T. tetragonioides shows potential for use as a functional food, with whitening and anti-wrinkle activities.

  7. The Cytolytic Amphipathic β(2,2-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma.

    Directory of Open Access Journals (Sweden)

    Liv-Marie Eike

    Full Text Available In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated cells. The use of a murine melanoma model demonstrated that the majority of animals treated with intratumoural injections of LTX-401 showed complete and long-lasting remission. Taken together, these results demonstrate the potential of LTX-401 as an immunotherapeutic agent for the treatment of solid tumors.

  8. The Cytolytic Amphipathic ?(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma

    OpenAIRE

    Eike, Liv-Marie; Mauseth, Brynjar; Camilio, Ketil Andr?; Rekdal, ?ystein; Sveinbj?rnsson, Baldur

    2016-01-01

    Published version. Source at http://doi.org/10.1371/journal.pone.0148980. License CC BY 4.0. In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treat...

  9. Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel.

    Science.gov (United States)

    Eshita, Yuki; Ji, Rui-Cheng; Onishi, Masayasu; Kobayashi, Takashi; Mizuno, Masaaki; Yoshida, Jun; Kubota, Naoji; Onishi, Yasuhiko

    2015-02-01

    The resistance of cancer cells to chemotherapeutic drugs (MDR) is a major problem to be solved. A supramolecular DEAE-dextran-MMA copolymer (DDMC)/paclitaxel (PTX) complex was obtained by using PTX as the guest and DDMC as the host having 50-300 nm in diameter. The drug resistance of B16F10 melanoma cells to paclitaxel was observed, but there is no drug resistance of melanoma cells to the DDMC/PTX complex in vitro. The cell death rate was determined using Michaelis-Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size, 50 nm), and DDMC/PTX5 (particle size, 290 nm) groups were 120 h (T/C, 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed the twofold effectiveness of PTX alone (p < 0.036). Histochemical analysis indicated that the administration of DDMC/PTX complex decreased distant metastasis and increased the survival of mice. A mouse of DDMC/PTX4 group in vivo was almost curing after small dermatorrhagia owing to its anti-angiogenesis, and it will be the hemorrhagic necrotic symptom of tumor by the release of "tumor necrosis factor alpha (TNF-α)" cytokine. As the result, the medicinal action of the DDMC/PTX complex will suppress the tumor-associated action of M2 macrophages and will control the metastasis of cancer cells.

  10. Penurunan Aktivitas Tirosinase dan Jumlah Melanin oleh Fraksi Etil Asetat Buah Malaka (Phyllantus emblica pada Mouse Melanoma B16 Cell-Line

    Directory of Open Access Journals (Sweden)

    Reti Hindritiani

    2013-06-01

    Full Text Available Melanin accumulation can lead to hyperpigmentation, and if it occurs on the face can cause psychosocial problem. Depigmenting agents derived from plants are increasingly utilized. Agents being developed have to be effective in inhibiting melanin synthesis and should not be toxic to melanocyte. This study aimed was to examine the effect of ethyl acetate fraction from Phyllanthus emblica (P. emblica fruit, also known as malaka fruit, towards melanine synthesis, which was measured from the melanin amount and tyrosinase activity, the key regulatory enzyme in melanin synthesis, spectrophotometrically towards melanocytes of mouse melanoma B16 cell-line. The cytotoxic effect towards melanocytes was measured with 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay. This study was conducted on November−December 2009 in Department of Biochemistry and Diabetes Research Centre, Chonbuk National University Medical School, South Korea. The result of this study showed that tyrosinase activity and melanin amount decreased in a dose-dependent manner towards various concentrations of ethyl acetate fraction of P. emblica fruit with inhibition concentration (IC 50=95.63 and 16.90 μg/mL, respectively and lethal dose (LD 50 concentration 106.64 μg/mL. In conclusion, ethyl acetate fraction of P. emblica fruit is a potential depigmenting agent, since it can reduce melanin synthesis by inhibition of tyrosinase activity.

  11. Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells.

    Science.gov (United States)

    Soni, Naina; Jyoti, Kiran; Jain, Upendra Kumar; Katyal, Anju; Chandra, Ramesh; Madan, Jitender

    2017-06-01

    Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells. Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals were prepared separately by precipitation method. The mean particle size of Nos-Ag 2+ nanocrystals was measured to be 25.33±3.52nm, insignificantly (P>0.05) different from 27.43±4.51nm of Red-Br-Nos-Ag 2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag 2+ nanocrystals was determined to be -25.3±3.11mV significantly (Pmelanoma cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells.

    Science.gov (United States)

    Nakamura, Seikou; Nakashima, Souichi; Tanabe, Genzo; Oda, Yoshimi; Yokota, Nami; Fujimoto, Katsuyoshi; Matsumoto, Takahiro; Sakuma, Rika; Ohta, Tomoe; Ogawa, Keiko; Nishida, Shino; Miki, Hisako; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

    2013-02-01

    Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (-)-lirinidine, and 2-hydroxy-1-methoxy-6a,7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine- and benzylisoquinoline-type alkaloids. In addition, 3-30 μM nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3-30 μM N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10-30 μM nuciferine inhibited the expression of TRP-2 mRNA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Lucas E.B., E-mail: lucasebsouza@usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Almeida, Danilo C., E-mail: gudaalmeida@gmail.com [Department of Medicine – Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP (Brazil); Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com [Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo (Brazil); Covas, Dimas T., E-mail: dimas@fmrp.usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br [Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2016-07-15

    The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced

  14. Andrographolide induces apoptosis in B16F-10 melanoma cells by inhibiting NF-κB-mediated bcl-2 activation and modulating p53-induced caspase-3 gene expression.

    Science.gov (United States)

    Pratheeshkumar, P; Sheeja, K; Kuttan, Girija

    2012-02-01

    Cancer is a disorder characterized by uncontrolled proliferation and reduced apoptosis. Inducing apoptosis is an efficient method of treating cancers. In this study, we investigated the effect of andrographolide on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of andrographolide showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays also confirmed the observation. The proapoptotic genes p53, Bax, caspase-9, and caspase-3 were found upregulated in andrographolide-treated cells, whereas the antiapoptotic gene bcl-2 was downregulated. This study also reveals that andrographolide treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB (NF-κB), and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells. These results suggest that andrographolide induces apoptosis via inhibiting NF-κB-induced bcl-2-mediated survival signaling and modulating p53-induced caspase-3-mediated proapoptotic signaling.

  15. Mixture of trypsin, chymotripsin and papain reduces formation of metastases and extends survival time of C57BL6 mice with syngeneic melanoma B16

    Czech Academy of Sciences Publication Activity Database

    Wald, M.; Olejár, T.; Šebková, V.; Zadinová, M.; Boubelík, Michael; Poučková, P.

    2001-01-01

    Roč. 47, - (2001), s. 16-22 ISSN 0344-5704 Institutional research plan: CEZ:AV0Z5052915 Keywords : proteolytic enzymes * metastasis * melanoma Subject RIV: EC - Immunology Impact factor: 2.170, year: 2001

  16. Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha.

    Science.gov (United States)

    Tsai, Chin-Shaw Stella; Luo, Shue-Fen; Ning, Chung-Chu; Lin, Chien-Liang; Jiang, Ming-Chung; Liao, Ching-Fong

    2009-08-01

    Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.

  17. Cáncer, inflamación y depresión: alteraciones conductuales, inmunitarias y neuroquímicas producidas por el desarrollo de melanoma B16 en ratones macho

    OpenAIRE

    Lebeña Maluf, Florencia Andrea

    2017-01-01

    275 p. Existe una gran cantidad de datos en el ámbito de la Psiconeuroinmunología que evidencian que la activación del sistema inmunitario provoca una respuesta sistémica de inflamación que contribuye al desarrollo de síntomas depresivos. El objetivo de este trabajo es estudiar los cambios inmunitarios, fisiológicos y conductuales asociados al desarrollo tumoral de melanoma B16, y determinar si una situación de estrés agudo, altera dichos cambios. Para ello se han utilizando dos cepas de r...

  18. Accumulation of cytolytic CD8{sup +} T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Min Sook [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Woo, Min-Yeong [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Department of Biomedical Sciences, The Graduate School, Ajou University (Korea, Republic of); Kwon, Daeho [Department of Microbiology, Kwandong University College of Medicine, Gangneung, Gangwon-do 210-701 (Korea, Republic of); Hong, Allen E. [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Song, Kye Yong [Department of Pathology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul 156-756 (Korea, Republic of); Park, Sun [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Lim, In Kyoung [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of)

    2014-10-01

    In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT) cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8{sup +} T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B{sup +} CD8{sup +} T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a{sup +} CD8{sup +} T cells in the splenocytes of KO mice may affect the loss of CD8{sup +} T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B{sup +} CD8{sup +} T-cells and CD107a{sup +} CD8{sup +} T-cells, thus transiently regulating in vivo anti-tumor immunity. - Highlights: • Constitutive expression of TIS21 in splenocytes and upregulation by TCR stimulation. • Proliferation of mature T-cells in spleen of TIS21KO mice after TCR stimulation. • Inhibition of cell death in mature T-cells of TIS21KO mice compared with the wild type. • Inhibition of melanoma growth in TIS21KO mice and CD8{sup +} T cell infiltration in tumor. • Reduction of CD 107{sup +}CD8{sup +} T cells, but increased granzyme B{sup +} CD8{sup +} T cells in TIS21KO mice.

  19. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors.

    Science.gov (United States)

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies.

  20. Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C(57)Bl(6) mice with syngeneic melanoma B16

    Czech Academy of Sciences Publication Activity Database

    Wald, M.; Olejar, T.; Šebková, V.; Zadinová, M.; Boubelík, Michael; Poučková, P.

    2001-01-01

    Roč. 47, - (2001), s. S16-S22 ISSN 0344-5704 Institutional research plan: CEZ:AV0Z5052915 Keywords : proteolytic enzymes * proteinases * transplantation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.170, year: 2001

  1. Melanoma

    Science.gov (United States)

    ... Lentigo maligna melanoma; Melanoma in situ; Superficial spreading melanoma; Nodular melanoma; Acral lentiginous melanoma ... and brown. It is most common in Caucasians. Nodular melanoma usually starts as a raised area that is ...

  2. β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.

    Science.gov (United States)

    Jung, Jae In; Kim, Eun Ji; Kwon, Gyoo Taik; Jung, Yoo Jin; Park, Taesung; Kim, Yongkang; Yu, Rina; Choi, Myung-Sook; Chun, Hyang Sook; Kwon, Seung-Hae; Her, Song; Lee, Ki Won; Park, Jung Han Yoon

    2015-09-01

    We reported previously that high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities. To examine whether BCP inhibits HFD-induced melanoma progression, 4-weeks old, male C57BL/6N mice were fed a control diet (CD, 10 kcal% fat) or HFD (60 kcal% fat + 0, 0.15 or 0.3% BCP) for the entire experimental period. After 16 weeks of feeding, B16F10s were subcutaneously injected into mice. Three weeks later, tumors were resected, and mice were killed 2 weeks post-resection. Although HFD feeding increased body weight gain, fasting blood glucose levels, solid tumor growth, LN metastasis, tumor cell proliferation, angiogenesis and lymphangiogenesis, it decreased apoptotic cells, all of which were suppressed by dietary BCP. HFD feeding increased the number of lipid vacuoles and F4/80+ macrophage (MΦ) and macrophage mannose receptor (MMR)+ M2-MΦs in tumor tissues and adipose tissues surrounding the LN, which was suppressed by BCP. HFD feeding increased the levels of CCL19 and CCL21 in the LN and the expression of CCR7 in the tumor; these changes were blocked by dietary BCP. In vitro culture results revealed that BCP inhibited lipid accumulation in 3T3-L1 preadipocytes; monocyte migration and monocyte chemoattractant protein-1 secretion by B16F10s, adipocytes and M2-MΦs; angiogenesis and lymphangiogenesis. The suppression of adipocyte and M2-cell accumulation and the inhibition of CCL19/21-CCR7 axis may be a part of mechanisms for the BCP suppression of HFD-stimulated melanoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Ethyl acetate extract from Panax ginseng C.A. Meyer and its main constituents inhibit α-melanocyte-stimulating hormone-induced melanogenesis by suppressing oxidative stress in B16 mouse melanoma cells.

    Science.gov (United States)

    Jiang, Rui; Xu, Xiao-Hao; Wang, Ke; Yang, Xin-Zhao; Bi, Ying-Fei; Yan, Yao; Liu, Jian-Zeng; Chen, Xue-Nan; Wang, Zhen-Zhong; Guo, Xiao-Li; Zhao, Da-Qing; Sun, Li-Wei

    2017-08-17

    Hyperpigmentation disease involves darkening of the skin color due to melanin overproduction. Panax ginseng C.A. Meyer is a well-known traditional Chinese medicine and has a long history of use as a skin lightener to inhibit melanin formation in China, Korea and some other Asian countries. However, the constituents and the molecular mechanisms by which they affect melanogenesis are not fully clear. The purpose of this study was to identify the active ingredient in Panax ginseng C.A. Meyer extract that inhibits mushroom tyrosinase activity and to investigate the antioxidative capacity and molecular mechanisms of the effective extract on melanogenesis in B16 mouse melanoma cells. Aqueous extracts of Panax ginseng C.A. Meyer were successively fractionated with an equal volume of chloroform, ethyl acetate, and n-butyl alcohol to determine the effects by examining the activity of mushroom tyrosinase. The effective fraction was analyzed using HPLC and LC-MS. The antioxidative capacity and the inhibitory effects on melanin content, cell intracellular tyrosinase activity, and melanogenesis protein levels were determined in α-melanocyte-stimulating hormone (α-MSH)-treated B16 mouse melanoma cells. The ethyl acetate extract from Panax ginseng C.A. Meyer (PG-2) had the highest inhibiting effect on mushroom tyrosinase, mainly contained phenolic acids, including protocatechuic acid, vanillic acid, p-coumaric acid, salicylic acid, and caffeic acid, and exhibited apparent antioxidant activity in vitro. PG-2 and its main constituents significantly decreased melanin content, suppressed cellular tyrosinase activity, and reduced expression of tyrosinase protein to inhibit B16 cells melanogenesis induced by α-MSH, and no cytotoxic effects were observed. They also inhibited cellular reactive oxygen species (ROS) generation, increased superoxide dismutase (SOD) activity and glutathione (GSH) level in α-MSH-treated B16 cells effectively. And those activities of its main constituents

  4. No increase of melanoma after kidney transplantation in the northern part of The Netherlands

    NARCIS (Netherlands)

    Bastiaannet, Esther; Heide, Jaap J. Homan-van der; Ploeg, Rutger J.; Hoekstra, Harald J.

    2007-01-01

    One medical problem of renal transplant patients who receive immuncisuppression therapy is the development of a malignancy during the long-term follow-up. Existing studies, however, are not in agreement over whether patients who undergo renal transplantation have an increased risk of melanoma. The

  5. Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim, E-mail: jim.xiang@saskcancer.ca

    2013-08-16

    Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

  6. Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

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    Fox Bernard A

    2007-11-01

    Full Text Available Abstract Background The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5 melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-γ or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN, were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-γ or TNF-α was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO was determined using GRIES reagent. Results We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1α and MIP-1β following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-γ or TNF-α, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC, MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin

  7. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

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    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  8. Glucocorticoid receptor knockdown decreases the antioxidant protection of B16 melanoma cells: an endocrine system-related mechanism that compromises metastatic cell resistance to vascular endothelium-induced tumor cytotoxicity.

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    Obrador, Elena; Valles, Soraya L; Benlloch, María; Sirerol, J Antoni; Pellicer, José A; Alcácer, Javier; Coronado, Javier Alcácer-F; Estrela, José M

    2014-01-01

    We previously reported an interorgan system in which stress-related hormones (corticosterone and noradrenaline), interleukin-6, and glutathione (GSH) coordinately regulate metastatic growth of highly aggressive B16-F10 melanoma cells. Corticosterone, at levels measured in tumor-bearing mice, also induces apoptotic cell death in metastatic cells with low GSH content. In the present study we explored the potential role of glucocorticoids in the regulation of metastatic cell death/survival during the early stages of organ invasion. Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in metastatic cells in vivo independent of the tumor location (liver, lung, or subcutaneous). The decrease in γ-GCS activity was associated with lower intracellular GSH levels. Nrf2- and p53-dependent down-regulation of γ-GCS was associated with a decrease in the activities of superoxide dismutase 1 and 2, catalase, glutathione peroxidase, and glutathione reductase, but not of the O2--generating NADPH oxidase. The GCR knockdown-induced decrease in antioxidant protection caused a drastic decrease in the survival of metastatic cells during their interaction with endothelial cells, both in vitro and in vivo; only 10% of cancer cells attached to the endothelium survived compared to 90% survival observed in the controls. This very low rate of metastatic cell survival was partially increased (up to 52%) in vivo by inoculating B16-F10 cells preloaded with GSH ester, which enters the cell and delivers free GSH. Taken together, our results indicate that glucocorticoid signaling influences the survival of metastatic cells during their interaction with the vascular endothelium.

  9. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  10. Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma

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    Ursa Lampreht Tratar

    2017-01-01

    Full Text Available Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12 into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12 in mice bearing aggressive B16F10 murine melanoma. IL-12 electrotransfer resulted in the complete long-term eradication of the tumors. Serum mIL-12 and murine interferon γ (mIFNγ were increased after IL-12 gene electrotransfer. Further on, hematoxylin and eosin (HE staining showed increased infiltration of immune cells that lasted from day 4 until day 14. Immunohistochemistry (IHC staining of F4/80, MHCII, and CD11c showed higher positive staining in the IL-12 gene electrotransfer group than in the control groups. Immune cell infiltration into the tumors and the high density of MHCII- and CD11c-positive cells suggest an antitumor polarization of macrophages and the presence of antigen-presenting cells that contributes to the important antitumor effectiveness of IL-12.

  11. Donor-derived metastatic melanoma in a liver transplant recipient established by DNA fingerprinting.

    Science.gov (United States)

    Bilal, Muhammad; Eason, James D; Das, Kanak; Sylvestre, Pamela B; Dean, Amanda G; Vanatta, Jason M

    2013-10-01

    Metastatic melanoma is a donor-derived malignancy that has rarely been reported in liver allograft recipients. We present a case of a transmitted donor-derived melanoma to a liver allograft recipient in whom the diagnosis was established by polymerase chain reaction-based DNA fingerprinting. A 52-year-old African-American man underwent a successful orthotropic liver transplant for alcohol-induced cirrhosis. One year after the orthotropic liver transplant, he presented at our institution with diffuse abdominal pain, and a computed tomography scan of the abdomen and chest showed innumerable masses diffusely involving the liver and multiple subcutaneous nodules in the abdominal and chest wall. A liver biopsy confirmed the diagnosis of metastatic melanoma. The origin of melanoma was traced to the donor by DNA fingerprinting of the native liver, the donor liver, and the donor gallbladder. Chemotherapy was initiated with temozolomide (75 mg/m² daily) and thalidomide (50 mg daily), to which he responded within 8 weeks with radiologic improvement in metastatic lesions. Tacrolimus was switched to sirolimus because of renal insufficiency as well as reported effectiveness against melanoma. Our patient survived for 9 months after the diagnosis of metastatic melanoma. He ultimately died of brain metastases. Donor-derived metastatic melanoma is a rare cancer with the highest transmission and mortality rates, which requires better recognition. Prompt diagnosis of donor-derived melanoma is critical and can be achieved reliably with polymerase chain reaction-based DNA analysis. Management options after diagnosis include de-escalation of immunosuppression, with or without urgent organ removal or retransplant. The roles of chemotherapy, immunotherapy, and radiotherapy require further study.

  12. Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin.

    Science.gov (United States)

    Peng, Li-Hua; Liu, Shuai; Xu, Shen-Yao; Chen, Lei; Shan, Ying-Hui; Wei, Wei; Liang, Wen-Quan; Gao, Jian-Qing

    2013-09-15

    Salidroside, the major active component of Rhodiola rosea, a herb with antioxidant, free radical scavenging and tyrosinase inhibitory effects, has been recently reported in protecting the kerationcytes from the UV radiation, suggesting the potential of this component in depigmentation. Paeonol is isolated from Moutan Cortex Radicis with anti-inflammation/microbial activities, was reported to induce the down-regulation of microphthalmia-associated transcription factor and subsequently tyrosinase. To testify the potential of these compounds as melanin formation inhibitors for hyperpigmentation therapy, the influence of salidroside and paeonol on pigmentation was investigated. With arbutin as a positive control, salidroside and paeonol were evaluated for their inhibitory effect on the cell viability, tyrosinase activity and melanin synthesis in B16F10 melanoma cells, as well as their effects in UVB-induced hyperpigmentation in brown guinea pig skins. It was demonstrated that the significant inhibition of salidroside (33.0%) and paeonol (22.2-30.9%) on the tyrosinase activity is slightly lower than that of arbutin (18.4-44.7%). However, salidroside exhibited the dose-dependent inhibition (30.6-42.0%) in melanin synthesis at a low concentration of 100 μM, paeonol and arbutin expressed inhibition rates of 27.4-37.2% and 25.8-45.6% within 500-1000 μM. The in vivo topical application of these compounds was demonstrated to obviously decrease the hyperpigmentation on UVB stimulated guinea pig skin. This study provided the original evidence for the salidroside and paeonol as therapeutic agents for pigmentation disorder and skin lightening, with further clinical investigation of these compounds in the field of depigmentation was suggested. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. [Preliminary study on molecular mechanism of curcumine anti-mouse melanoma].

    Science.gov (United States)

    Gui, Fei; Ma, Wei-Feng; Cai, Shao-Hui; Li, Xiao-Kun; Tan, Yi; Zhou, Chun-Ling; Chen, Hong-Yuan

    2008-11-01

    To investigate the effects of curcumine on mouse B16 melanoma growth and possible mechanism of Bcl-2, P53 and glutathione in tumor cells. The inhibitory effect on growth of melanoma in vivo were examined by mice melanoma models transplanted B16 cells to C57BL/6J mice. MTT method was used to assay the contribution of curcumine to B16 cells in vitro. The apoptosis and expression of Bcl-2, P53 gene of B16 cells were analyzed by flow cytometry, and HPLC assay was used to detect the change of GSH in B16 melanom tissues of C57BL/6J mouse caused by curcumine. Curcumine had obvious inhibitory effect on the growth of mouse B16 melanoma in time and dose dependent manner and the gene expression of bcl-2 in B16 cells decreased after 24 hours supplied with curcumine, whereas P53 protein expression increased; Curcumine depressed the GSH quantity in melanoma tissues. The growth inhibitory effect of curcumine on mouse melanom is proved in vivo and in vitro respectively. Curcumine can induce some cells to apoptosis which may be relevant to downregulation of bcl-2 expression and upregulation of P53 expression as well as exhaustion of GSH in tumor organization.

  14. Amniotic Membrane Transplantation in Surgical Treatment of Conjunctival Melanoma: Long-term Results.

    Science.gov (United States)

    Palamar, Melis; Yaman, Banu; Akalın, Taner; Yağcı, Ayse

    2018-02-01

    To investigate the long-term efficacy and results of surgical management of conjunctival melanoma reconstructed with amniotic membrane transplantation. Conjunctival melanoma in 10 patients (5 female, 5 male) was totally excised with adjunctive cryotherapy to the surgical margins, corneal epitheliectomy with absolute alcohol in cases of corneal involvement, lamellar sclerectomy in cases with episcleral involvement, and ocular surface grafting with cryopreserved amniotic membrane. Complications and tumor control rates were evaluated. The mean age of the patients was 57.4±15.2 (range, 37-84) years. The mean diameter of the tumors was 15.5±4.9 (range, 10-25) mm and histopathologically confirmed complete excision was performed in all cases. Mild limbal stem cell deficiency (2 eyes) and subclinical symblepharon (3 eyes) were observed as long-term complications. In a mean follow-up of 56.7±40.4 (range, 30-132) months, only one local tumor recurrence was detected. Despite retreatment, exenteration was performed in this patient due to re-recurrence. One patient died due to disseminated metastasis despite the absence of local recurrence. In large conjunctival melanomas, reconstruction of the ocular surface is usually very challenging. The use of cryopreserved amniotic membrane for conjunctival defect repair is safe and effective with mild complications, and allows the excision of wider margins around the tumor.

  15. Amniotic Membrane Transplantation in Surgical Treatment of Conjunctival Melanoma: Long-term Results

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    Melis Palamar

    2018-02-01

    Full Text Available Objectives: To investigate the long-term efficacy and results of surgical management of conjunctival melanoma reconstructed with amniotic membrane transplantation. Materials and Methods: Conjunctival melanoma in 10 patients (5 female, 5 male was totally excised with adjunctive cryotherapy to the surgical margins, corneal epitheliectomy with absolute alcohol in cases of corneal involvement, lamellar sclerectomy in cases with episcleral involvement, and ocular surface grafting with cryopreserved amniotic membrane. Complications and tumor control rates were evaluated. Results: The mean age of the patients was 57.4±15.2 (range, 37-84 years. The mean diameter of the tumors was 15.5±4.9 (range, 10-25 mm and histopathologically confirmed complete excision was performed in all cases. Mild limbal stem cell deficiency (2 eyes and subclinical symblepharon (3 eyes were observed as long-term complications. In a mean follow-up of 56.7±40.4 (range, 30-132 months, only one local tumor recurrence was detected. Despite retreatment, exenteration was performed in this patient due to re-recurrence. One patient died due to disseminated metastasis despite the absence of local recurrence. Conclusion: In large conjunctival melanomas, reconstruction of the ocular surface is usually very challenging. The use of cryopreserved amniotic membrane for conjunctival defect repair is safe and effective with mild complications, and allows the excision of wider margins around the tumor.

  16. Expression of CD44 on two lines of transplantable melanoma cells--relationship with cytokine secretion and tumor progression.

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    Sławomir Wójcik

    2004-03-01

    Full Text Available In the present work it was investigated if a spontaneous alteration of the native melanotic transplantable melanoma form into amelanotic form, connected with the tumor progression, is accompanied by changes of CD44 surface glycoprotein expression. We also tried to find out if there exists any correlation between changes in CD44 expression and IL-6, TNF-alpha, and IL-10 secretion. Cells of two hamster transplantable melanoma lines: melanotic and amelanotic were used. The levels of TNF-alpha, IL-6, IL-10 in supernatants were determined by the ELISA test. For the detection of CD44 expression by flow cytometry, isolated melanoma cells were stained with the rat anti-mouse CD44 monoclonal antibody. The stained cells were also examined using a fluorescence microscope and a confocal microscopy system. The obtained results indicate that a spontaneous alteration of the native melanotic form into amelanotic form and the associated tumor progression was accompanied by a decrease in CD44 glycoprotein expression on the cell surface and a decrease in IL-6, TNF-alpha and especially IL-10 secretion by amelanotic melanoma cells. Our observations suggest a relationship between CD44 expression and locally secreted cytokines in the course of transplantable melanoma progression.

  17. Non-melanoma skin cancer in renal transplant recipients: a study in a Brazilian reference center

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    Gonçalves CP

    2015-07-01

    Full Text Available Carolina Pereira Gonçalves, Beatriz Moritz Trope, Marcia Ramos-e-Silva Sector of Dermatology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Background: Non-melanoma skin cancer (NMSC after kidney transplantation is common and can result in significant morbidity and mortality. Their incidence and risk factors in renal transplant recipients (RTRs vary depending on geographic location and there is a scarcity of literature describing the features of NMSC in Brazil. Methods: NMSC data were retrospectively reviewed in charts of RTRs at the Clementino Fraga Filho University Hospital from January 2004 to December 2005, with the objectives of: 1 evaluating the occurrence of NMSC in RTRs transplanted between 2004 and 2005 at a reference center in Brazil; 2 verifying the frequency of basal cell carcinoma (BCC and squamous cell carcinoma (SCC in these patients according to sex, race, age, and tumor site; and 3 determining the time between transplantation and neoplasia. Results: We found 202 RTRs, with 165 suitable for the study. There were 19 NMSC in eleven patients (6.67%, at a mean time of 37.7 months after transplantation. The mean follow-up time was 72.7 months. The ratio of SCC:BCC was 1.1:1. White race and age ≥40 years were associated with a higher incidence of NMSC and they appeared predominantly in sun-exposed sites. Conclusion: Regular dermatological follow-up of RTRs can help to make earlier diagnoses, resulting in better quality of life and lower morbidity and mortality. Keywords: squamous cell carcinoma, basal cell carcinoma, Brazil 

  18. Melanoma

    Science.gov (United States)

    ... if they're dark skinned, young, and have no family history. Even for them, behaviors like too much sun exposure and not enough skin protection are important risk factors. How Do People Know They Have It? Many melanomas start out as a mole or a bump ...

  19. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).

    Science.gov (United States)

    Zwald, F; Leitenberger, J; Zeitouni, N; Soon, S; Brewer, J; Arron, S; Bordeaux, J; Chung, C; Abdelmalek, M; Billingsley, E; Vidimos, A; Stasko, T

    2016-02-01

    Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

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    Martyna Śniegocka

    2018-04-01

    Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

  1. PEG-b-PPS-b-PEI micelles and PEG-b-PPS/PEG-b-PPS-b-PEI mixed micelles as non-viral vectors for plasmid DNA: tumor immunotoxicity in B16F10 melanoma.

    Science.gov (United States)

    Velluto, Diana; Thomas, Susan N; Simeoni, Eleonora; Swartz, Melody A; Hubbell, Jeffrey A

    2011-12-01

    Cationic micelles formed from poly(ethylene glycol)-bl-poly(propylene sulfide)-bl-poly(ethylene imine) (PEG-b-PPS-b-PEI) and from mixtures of poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-b-PPS) with PEG-b-PPS-b-PEI were explored as non-viral vectors for plasmid DNA (pDNA) transfection in a tumor immunotoxicity model. Complexes with pDNA were found to be templated exclusively by the size of the pDNA-free micelles and ranged from 240 nm (for PEG-b-PPS-b-PEI) to 30 nm (for mixed micelles of PEG-b-PPS/PEG-b-PPS-b-PEI). Both formulations transfected melanoma cells well in vitro. As a model with a functional read-out of tumor cell death, one with likely only small bystander effects, tumors were transfected with an antigen transgene, using an antigen to which the recipient animals had been previously vaccinated with a Th1-biasing adjuvant. Reduction in tumor growth, increase in intratumoral infiltration of cytotoxic T lymphocytes and accumulation of Th1-biasing cytokines indicated that both micelle formulations transfected efficiently compared with naked pDNA and with low cytotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. 15 CFR 8b.16 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discrimination prohibited. 8b.16 Section 8b.16 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION... Accessibility § 8b.16 Discrimination prohibited. No qualified handicapped individual shall, because a recipient...

  3. Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers

    International Nuclear Information System (INIS)

    Veness, M. J.; Harris, D.

    2007-01-01

    Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered

  4. BFGF neutralization stimulates VEGF secretion in melanoma B16 cells.

    Science.gov (United States)

    Wang, Zhiyong; Wei, Pei; Xiang, Junjian; Wang, Hong

    2017-08-01

    Fusarium root rot is a major cryptogamic disease in olive trees caused by the soil-borne fungus Fusarium solani. Controlling this disease requires the extensive use of chemicals. However, using BCAs such as some Trichoderma strains may be an opportune alternative to fungicides in protecting olive plantations. A new isolate (Fso14) was isolated from young olive trees showing severe dieback symptoms. The objective of this work was to analyze the biocontrol behavior of a Tunisian strain of T. harzianum (Ths97) on olive trees against Fso14 by assessing both mycoparasitic activity (in planta and in vitro) and ability to locally modulate different gene-related defenses of the plant. Ths97 was found to inhibit Fso14 growth in vitro. Optical microscopic analysis at the confrontation zone between hyphae showed that Ths97 grew alongside Fso14 with numerous contact points suggesting parasitic activity. On olive trees, Ths97 developed a strong protective role against root infestation by Fso14, whether inoculated before or after the pathogenic agent. When inoculated alone, Fso14 and Ths97 did not modulate (or only slightly with inhibitions or inductions, respectively) the expression of genes involved in plant immunity (oxidative stress, phenylpropanoid pathway, PR-proteins and JA/Et-SA hormonal status). However, when Ths97 was inoculated in combination with Fso14, several defense-related genes were highly up-regulated, indicating probable primed-plant events. These promising results provided valuable information on using Ths97 as a beneficial agent to control fusarium root rot disease caused by F. solani in olive trees. Copyright © 2017. Published by Elsevier Ltd.

  5. An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

    Science.gov (United States)

    Kirby, L C; Banerjee, A; Augustine, T; Douglas, J F

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation. © 2016 British Association of Dermatologists.

  6. Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

    Science.gov (United States)

    Tanaka, Tomohiro; Voigt, Michael D

    2018-03-01

    Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r 2  = 0.971, p risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p risk of developing NMSC in the long-term after LT.

  7. Malignant melanoma of the conjunctiva – successful surgical excision of the primary tumor and reconstruction by conjunctival auto transplantation from the contralateral eye.

    Science.gov (United States)

    Sivkova, N; Chokoeva, A A; Dobrev, H; Staribratova, D; Belovezhdov, V; Tchernev, G; Wollina, U

    2014-01-01

    Malignant melanoma of the conjunctiva is a rare tumor with incidence of 0.5 cases/year per million population. It may also occur as de novo, as on the basis of preexisting melanocytic lesions (nevus or freckle) or most often from the so-called primary acquired melanosis of the conjuctiva (PAM). It metastasizes mainly lymphogenic and hematogenous. The size of the primary tumor lesion, histopathological findings and absolute tumor thickness are essential for unfavorable prognosis. Conjunctival auto transplantation from the other eye is modern and innovative, but also a seldomly feasible method of reconstruction after conjunctival excision of tumors in this area. We present a rare case of a 75-year-old patient with epithelioid cell malignant melanoma of the bulbar conjunctiva of the right eye, which de novo occurred, successfully treated by excision of the primary tumor and subsequent reconstruction by conjunctival auto transplant from the other eye. A very good therapeutic and aesthetic result was achieved.

  8. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  9. TRANSPLANTATION

    African Journals Online (AJOL)

    stage kidney disease. There is good evidence that transplantation improves both the quality and quantity of life in renal transplant recipients when compared with dialysis.1,2. Living donor kidney transplantation has gained popularity, not only owing ...

  10. Spontaneous Post-Transplant Disorders in NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac (NOG Mice Engrafted with Patient-Derived Metastatic Melanomas.

    Directory of Open Access Journals (Sweden)

    Enrico Radaelli

    Full Text Available Patient-derived tumor xenograft (PDTX approach is nowadays considered a reliable preclinical model to study in vivo cancer biology and therapeutic response. NOD scid and Il2rg-deficient mice represent the "gold standard" host for the generation of PDTXs. Compared to other immunocompromised murine lines, these mice offers several advantages including higher engraftment rate, longer lifespan and improved morphological and molecular preservation of patient-derived neoplasms. Here we describe a spectrum of previously uncharacterized post-transplant disorders affecting 14/116 (12% NOD.Cg- Prkdcscid Il2rgtm1Sug/JicTac (NOG mice subcutaneously engrafted with patient-derived metastatic melanomas. Affected mice exhibited extensive scaling/crusting dermatitis (13/14 associated with emaciation (13/14 and poor/unsuccessful tumor engraftment (14/14. In this context, the following pathological conditions have been recognized and characterized in details: (i immunoinflammatory disorders with features of graft versus host disease (14/14; (ii reactive lymphoid infiltrates effacing xenografted tumors (8/14; (iii post-transplant B cell lymphomas associated with Epstein-Barr virus reactivation (2/14. We demonstrate that all these entities are driven by co-transplanted human immune cells populating patient-derived tumor samples. Since the exploding interest in the utilization of NOD scid and Il2rg-deficient mice for the establishment of PDTX platforms, it is of uppermost importance to raise the awareness of the limitations associated with this model. The disorders here described adversely impact tumor engraftment rate and animal lifespan, potentially representing a major confounding factor in the context of efficacy and personalized therapy studies. The occurrence of these conditions in the NOG model reflects the ability of this mouse line to promote efficient engraftment of human immune cells. Co-transplanted human lymphoid cells have indeed the potential to

  11. A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis.

    Science.gov (United States)

    LaBerge, Greggory S; Duvall, Eric; Grasmick, Zachary; Haedicke, Kay; Pawelek, John

    2017-01-01

    Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma. Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML), developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes. DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor. The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease.

  12. A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis.

    Directory of Open Access Journals (Sweden)

    Greggory S LaBerge

    Full Text Available Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma.Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML, developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes.DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor.The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease.

  13. Targeting B16 tumors in vivo with peptide-conjugated gold nanoparticles

    Science.gov (United States)

    Poon, Wilson; Zhang, Xuan; Bekah, Devesh; Teodoro, Jose G.; Nadeau, Jay L.

    2015-07-01

    This study examines the effects of polyethylene glycol (PEG) and peptide conjugation on the biodistribution of ultrasmall (2.7 nm) gold nanoparticles in mice bearing B16 melanoma allografts. Nanoparticles were delivered intravenously, and biodistribution was measured at specific timepoints by organ digestion and inductively coupled plasma mass spectrometry. All major organs were examined. Two peptides were tested: the cyclic RGD peptide (cRGD, which targets integrins); and a recently described peptide derived from the myxoma virus. We found the greatest specific tumor delivery using the myxoma peptide, with or without PEGylation. Un-PEGylated cRGD performed poorly, but PEGylated RGD showed a significant transient collection in the tumor. Liver and kidney were the primary targets of all constructs. None of the particles were able to cross the blood-brain barrier. Although it was able to deliver Au to B16 cells, the myxoma peptide did not show any cytotoxic activity against these cells, in contrast to previous reports. These results indicate that the effect of passive targeting by PEGylation and active targeting by peptides can be independent or combined, and that they should be evaluated on a case-by-case basis when designing new nanosystems for targeted therapies. Both myxoma peptide and cRGD should be considered for specific targeting to melanoma, but a thorough investigation of the cytotoxicity of the myxoma peptide to different cell lines remains to be performed.

  14. Sesquiterpenes from fruits of Torilis japonica with inhibitory activity on melanin synthesis in B16 cells.

    Science.gov (United States)

    Song, Da Hye; Jo, Yang Hee; Ahn, Jong Hoon; Kim, Seon Beom; Yun, Cheong-Yong; Kim, Youngsoo; Hwang, Bang Yeon; Lee, Mi Kyeong

    2018-01-01

    Melanin, a dark macromolecular pigment, protects skin from harmful damage. However, abnormal accumulation is responsible for hyperpigmentation disorders. Melanogenesis inhibitors have therefore become important constituents in cosmetic products for depigmentation. Torilis japonica Decandolle (Umbelliferae) is a biennial plant which is distributed in East Asia. Fruits of this plant have been used for the treatment of skin disease and inflammation. In our previous study, torilin, a major sesquiterpene of T. japonica, showed an inhibitory effect on melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells. Further extensive chromatographic separation resulted in thirteen compounds. On the basis of spectroscopic analysis, the structures of the compounds isolated were determined to be three new sesquiterpenes, viz. a guaiane-type, epoxytorilinol (1), a eudesmane-type, elematorilone (2) and a cadinane-type, cardinatoriloside (3), together with ten known sesquiterpenes (4-13). Of the compounds isolated, compounds 4-6 and 11-13 inhibited α-MSH-activated melanin production in B16 melanoma cells with IC 50 values from 72.9 to 191.0 μM.

  15. Radix Astragali and Tanshinone Help Carboplatin Inhibit B16 Tumor Cell Growth.

    Science.gov (United States)

    Wu, Jinyi; Xu, Haiming; Zhang, Lei; Zhang, Xiuying

    2016-08-01

    Excessive UV radiation causes increased melanoma incidence. Postoperation chemotherapy will destroy lymphocytes and compromise immune response. Immunodepression is also detected in patients with cancers. Previous studies suggested that polysaccharide-protein complexes manifested immunomodulatory and antitumor activities. Radix Astragali (RA) extract is a product of polysaccharide-protein complexes, which has been used in the treatment of a variety of diseases because of its low toxicity to the host. Tanshinone (TA) is a derivative of phenanthrenequinone isolated from Danshen, which is suggested to inhibit tumor growth by inducing apoptosis in tumor cells. Carboplatin (CA) is a commonly used chemotherapeutic drug in melanoma treatment. Therefore, we hypothesized that the combination of RA and TA will help CA better inhibit the B16 cell growth. The study will test that the efficacy of growth inhibition of tumor cell produced by CA + RA + TA is better than CA + RA or CA + TA. The B16 tumor cells were injected to Swiss-Hauschka (ICR) mice subcutaneously. Twenty-four hours later, mice received CA intraperitoneally, CA + RA (RA were administered gastrically at the dosage of 10 g/kg body weight), CA + TA (TA were administered gastrically at the dosage of 0.5 g/kg body weight), or no treatment (model group). Tumor weight, volume, latency, incidence, the percentage of CD4(+) and CD8(+) in spleen, and natural killer (NK), and cytotoxic lymphocyte (CTL) activities were measured and compared among different groups. Compared with mice treated with CA + RA, CA + TA, or CA alone, the mice treated with CA + RA + TA showed (1) significantly smaller tumor weight and tumor volume; (2) significantly longer tumor latency; (3) significantly lower tumor incidence; and (4) significantly increased percentage of CD4(+) and CD8(+) in spleen and increased activities of NK and CTL. Combination of RA and TA can help CA produce more effective inhibition on B16 cell growth. © The Author(s) 2015.

  16. Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

    Directory of Open Access Journals (Sweden)

    E. A. Korchuganova

    2013-01-01

    Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

  17. Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

    Directory of Open Access Journals (Sweden)

    E. A. Korchuganova

    2014-07-01

    Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

  18. Asiaticoside, a component of Centella asiatica, inhibits melanogenesis in B16F10 mouse melanoma.

    Science.gov (United States)

    Kwon, Ku Jung; Bae, Seunghee; Kim, Karam; An, In Sook; Ahn, Kyu Joong; An, Sungkwan; Cha, Hwa Jun

    2014-07-01

    Melanogenesis is the process of generating pigmentation via melanin synthesis and delivery. Three key enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1) and TRP2, metabolize melanin from L-tyrosine. Melanin synthesizing enzymes are regulated by microphthalmia-associated transcription factor (MITF). The titrated extract of Centella asiatica (TECA) contains the major components asiatic acid, asiaticoside and madecassic acid. The present study revealed that TECA reduces the melanin content in melanocytes. Moreover, the asiaticoside contained in TECA modulated melanogenesis by inhibiting tyrosinase mRNA expression. The decrease in tyrosinase mRNA levels was mediated through MITF. Uniquely, asiaticoside inhibited MITF by decreasing its DNA binding affinity. In conclusion, the results of the present study indicate that asiaticoside treatment may have beneficial effects in hyperpigmentation diseases or for skin whitening.

  19. C5 Extract Induces Apoptosis in B16F10 Murine Melanoma Cells ...

    African Journals Online (AJOL)

    Bio/Molecular Informatics Center, Konkuk University, 3BanryongInsu Herb Clinic, Nonhyun-dong, Kangnam-ku, Seoul, 4Sunwun. Biophysic, Ansung ... 6Genomic Informatics Center, Hankyong National University, Anseong, Gyeonggi-do, Republic of Korea ..... from the Korean Health Technology R&D Project,. Ministry of ...

  20. Activation of peritoneal macrophages to cytoxicity against B16 melanoma cells by Serratia marcescens polyribosome fractions

    International Nuclear Information System (INIS)

    Hoover, S.K.

    1985-01-01

    Serratia marcescens polyribosomes (SMPR) have been shown to elicit an anti-tumor response in vivo. The in-vitro effects of SMPR on macrophages as the nonspecific mediators of the anti-tumor response have not previously been examined. The first objective of this research project is to corroborate and analyze the in-vivo results by the development and application of an in-vitro cytotoxicity assay. The second objective is to examine the effect of SMPR upon previously unstimulated peritoneal macrophages as representing the mechanism of cytotoxicity. The third objective is to identify the minimal effective component of SMPR responsible for an effect on macrophages. Results revealed that SMPR preparations exert a number of effects upon macrophages. Morphologic changes included increased spreading and increased perinuclear vacuolization. Macrophages were shown to be metabolically activate by two lines of evidence. SMPR-treated macrophages exhibited increased cellular metabolism by the increased uptake of 3 H-thymidine and by the increased levels of secreted leucine aminopeptidase as compared to control macrophages. Results also showed that SMPR activates macrophages to cytotoxicity against syngeneic tumor target cells. Buoyant-density fractions were isolated and assayed for macrophage activating ability. Results showed 50S ribosomal subunits to be the smallest fraction effective for macrophage activation. Both the RNA and protein were necessary for complete effectiveness

  1. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF in mouse melanoma B16F10 in vivo

    Directory of Open Access Journals (Sweden)

    Kranjc Simona

    2016-03-01

    Full Text Available Pulsed electromagnetic field (PEMF induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery.

  2. Diterpenoid B derived from Plectranthus excisus inhibits the melanoma cell cycle in the B16 melanoma cell line.

    Science.gov (United States)

    Liu, Ya-Nan; Gu, Jun-Lian; Ma, Meng-Shi; Guo, Hua; Liu, Long; Guo, Li-Rong; Wang, Yue; Li, Yang

    2015-09-01

    Plectranthus excisus is widely distributed throughout northeast China. Its active ingredient, diterpenoids, exhibits significant antitumor effects. The present study examined the antitumor effects of diterpenoid B (DB), derived from Plectranthus excisus, and demonstrated that DB inhibited the proliferation of tumor cells by inhibiting the cell cycle. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to determine mRNA and protein expression levels, respectively. The results revealed that exposure to DB increased the expression levels of the transformation associated, protein 53, and cyclin‑dependent kinase inhibitor 1A, and decreased the expression of cyclin‑dependent kinase 2. The results of the present study demonstrated that DB can inhibit cell cycle progression and, therefore, offers potential as a beneficial antitumor drug.

  3. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  4. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    International Nuclear Information System (INIS)

    Misu, Masayasu; Ouji, Yukiteru; Kawai, Norikazu; Nishimura, Fumihiko; Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2015-01-01

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage

  5. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Misu, Masayasu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ouji, Yukiteru, E-mail: oujix@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Kawai, Norikazu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nishimura, Fumihiko [Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nakamura-Uchiyama, Fukumi [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Yoshikawa, Masahide, E-mail: myoshika@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2015-08-07

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage.

  6. Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis.

    Science.gov (United States)

    Khosrotehrani, Kiarash; Nguyen Huu, Sau; Prignon, Aurélie; Avril, Marie-Françoise; Boitier, Françoise; Oster, Michèle; Mortier, Laurent; Richard, Marie-Aleth; Maubec, Eve; Kerob, Delphine; Mansard, Sandrine; Merheb, Charbel; Moguelet, Philippe; Nassar, Dany; Guégan, Sarah; Aractingi, Selim

    2011-04-01

    The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity.

    Directory of Open Access Journals (Sweden)

    Marta Stasiak

    Full Text Available Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1 melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.

  8. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

    The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. Selected literature. About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing

  9. 17 CFR 240.10b-16 - Disclosure of credit terms in margin transactions.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Disclosure of credit terms in margin transactions. 240.10b-16 Section 240.10b-16 Commodity and Securities Exchanges SECURITIES AND... § 240.10b-16 Disclosure of credit terms in margin transactions. (a) It shall be unlawful for any broker...

  10. 26 CFR 31.3121(b)(16)-1 - Services performed under share-farming arrangement.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Services performed under share-farming arrangement. 31.3121(b)(16)-1 Section 31.3121(b)(16)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Revenue Code of 1954) General Provisions § 31.3121(b)(16)-1 Services performed under share-farming...

  11. Ocular Melanoma

    Science.gov (United States)

    ... also occur on the conjunctiva . Because most eye melanomas form in the part of the eye you can’t see when looking in a mirror, they can be difficult to detect. Also, eye melanoma typically doesn’t cause early signs or symptoms . ...

  12. Malignant melanoma

    NARCIS (Netherlands)

    de Braud, Filippo; Khayat, David; Kroon, Bin B. R.; Valdagni, Riccardo; Bruzzi, Paolo; Cascinelli, Natale

    2003-01-01

    In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk

  13. Caloric restriction induces heat shock response and inhibits B16F10 cell tumorigenesis both in vitro and in vivo

    Science.gov (United States)

    Novelle, Marta G.; Davis, Ashley; Price, Nathan L.; Ali, Ahmed; Fürer-Galvan, Stefanie; Zhang, Yongqing; Becker, Kevin; Bernier, Michel; de Cabo, Rafael

    2015-01-01

    Caloric restriction (CR) without malnutrition is one of the most consistent strategies for increasing mean and maximal lifespan and delaying the onset of age-associated diseases. Stress resistance is a common trait of many long-lived mutants and life-extending interventions, including CR. Indeed, better protection against heat shock and other genotoxic insults have helped explain the pro-survival properties of CR. In this study, both in vitro and in vivo responses to heat shock were investigated using two different models of CR. Murine B16F10 melanoma cells treated with serum from CR-fed rats showed lower proliferation, increased tolerance to heat shock and enhanced HSP-70 expression, compared to serum from ad libitum-fed animals. Similar effects were observed in B16F10 cells implanted subcutaneously in male C57BL/6 mice subjected to CR. Microarray analysis identified a number of genes and pathways whose expression profile were similar in both models. These results suggest that the use of an in vitro model could be a good alternative to study the mechanisms by which CR exerts its anti-tumorigenic effects. PMID:25948793

  14. The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice.

    Science.gov (United States)

    Manjamalai, A; Grace, V M Berlin

    2013-01-01

    Current investigation is to evaluate the anticancer activity of the essential oil of Plectranthus amboinicus (Lour) on B16F-10 melanoma cell line injected C57BL/6 mice, and it was simultaneously treated with the essential oil of P. amboinicus (Lour) (50 μg/dose) via i.p. for 21 days. The present investigation exhibited the potent chemotherapeutic/chemopreventive effect of the essential oil of P. amboinicus (Lour) over lung metastasis that developed. To our knowledge, this is the first report in evaluating the effect of essential oil of P. amboinicus (Lour) using lung cancer model.

  15. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  16. Up-Regulation of Hepatoma-Derived Growth Factor Facilities Tumor Progression in Malignant Melanoma

    Science.gov (United States)

    Kung, Mei-Lang; Liu, Li-Feng; Kuo, Lai-Hsin; Kuo, Hsiao-Mei; Chen, San-Cher; Chan, Elsa C.; Wu, Chieh-Shan; Tai, Ming-Hong; Liu, Guei-Sheung

    2013-01-01

    Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16–F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma. PMID:23536873

  17. CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway.

    Science.gov (United States)

    Trimmer, Casey; Whitaker-Menezes, Diana; Bonuccelli, Gloria; Milliman, Janet N; Daumer, Kristin M; Aplin, Andrew E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P; Capozza, Franco

    2010-10-01

    Caveolin-1 (CAV1) is the main structural component of caveolae, which are plasma membrane invaginations that participate in vesicular trafficking and signal transduction events. Although evidence describing the function of CAV1 in several cancer types has recently accumulated, its role in melanoma tumor formation and progression remains poorly explored. Here, by using B16F10 melanoma cells as an experimental system, we directly explore the function of CAV1 in melanoma tumor growth and metastasis. We first show that CAV1 expression promotes proliferation, whereas it suppresses migration and invasion of B16F10 cells in vitro. When orthotopically implanted in the skin of mice, B16F10 cells expressing CAV1 form tumors that are similar in size to their control counterparts. An experimental metastasis assay shows that CAV1 expression suppresses the ability of B16F10 cells to form lung metastases in C57Bl/6 syngeneic mice. Additionally, CAV1 protein and mRNA levels are found to be significantly reduced in human metastatic melanoma cell lines and human tissue from metastatic lesions. Finally, we show that following integrin activation, B16F10 cells expressing CAV1 display reduced expression levels and activity of FAK and Src proteins. Furthermore, CAV1 expression markedly reduces the expression of integrin β(3) in B16F10 melanoma cells. In summary, our findings provide experimental evidence that CAV1 may function as an antimetastatic gene in malignant melanoma. © 2010 AACR.

  18. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry......The purpose of this study was to develop a suitable animal model for the investigation of the pathogenesis and therapy of uveal malignant melanoma. Eight choroidal malignant melanomas from eight patients were transplanted into nude mice in an attempt to establish a serially transplantable tumour...... the characteristic properties of malignant melanoma. However, the transplanted cells demonstrated vimentin reactivity, whereas the primary tumour cells were negative for vimentin. It can be concluded that a new experimental model of malignant uveal melanoma with tumours that were easy to observe and access...

  19. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  20. Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report).

    OpenAIRE

    E. A. Korchuganova; A. Yu. Slonimskiy,; O. Yu. Yatsenko; M. Yu. Lerner

    2013-01-01

    There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0) on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vas...

  1. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail: sbeebe@odu.edu; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  2. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    Beebe, Stephen J.; Schoenbach, Karl H.; Heller, Richard

    2010-01-01

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma

  3. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller

    2010-09-01

    Full Text Available Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs. EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  4. Uveal Melanoma

    International Nuclear Information System (INIS)

    Papastefanou, V. P.; Cohen, V. M. L.; Cohen, V. M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future

  5. Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines

    Directory of Open Access Journals (Sweden)

    Akram Jamshidzadeh

    2017-10-01

    Full Text Available Context: One of the most complained skin cares in ethnic skin like Asian women is hyperpigmentation, and lightening preparations have been long-standing desired. Due to the side effects of current drugs, medicinal plants have attracted more attentions as a source of novel drugs. Mazo (Quercus infectoria galls and Terminalia chebula fruits have been suggested in Persian Traditional Medicine as a safe treatment for hyperpigmentation. Aims: To evaluate the cytotoxicity and the effect on melanin synthesis in B16/F10 melanoma of Q. infectoria and T. chebula extracts. Methods: After collection and scientific authentication, plants were extracted by maceration method with methanol and were standardized based on total phenolic content. MTT assay and colorimetric method were used for cytotoxicity and determination of melanin content and tyrosinase activity in B16/F10 cells, respectively. Kojic acid was used as a reference compound. Results: Total phenolic content of Q. infectoria and T. chebula was determined as 287.34 ± 4.21 and 172.61 ± 8.67 mg gallic acid equivalent/g dried extract, respectively. Both plants decreased cell viability at 100 µg/mL and significantly reduced intercellular melanin to 66.25% and 71.1%, respectively in comparison to kojic acid (56.63% at 50 µg/mL. In the same concentration, 65.7% and 71.2% tyrosinase activity was inhibited by Q. infectoria and T. chebula, which significantly were different from control (p<0.001. Conclusions: These findings suggest that both plants especially Q. infectoria could inhibit melanogenesis in non-toxic concentrations and would be a good candidate for further studies.

  6. Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?

    DEFF Research Database (Denmark)

    Jung, Ji-Won; Overgaard, Nana H; Burke, Michael T

    2016-01-01

    Patients receiving immunosuppression to prevent organ transplant rejection are at a greatly increased risk of developing nonmelanoma skin cancer. In recent years a correlation has been identified between the class of immunosuppressant that these patients receive and their subsequent cancer risk; ...

  7. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  8. The application of quantum dots for the melanoma tumor in vivo imaging

    Science.gov (United States)

    Feng, Yayi; Zhai, Peng; Wang, Xiaomei; Ying, Ming; Wu, Jinbo; Zhu, Xiaomei; Lin, Guimiao; Chen, Qiang; Xu, Gaixia

    2014-09-01

    Objective: Over the past decade, fluorescent semiconductor nanocrystals, also known as quantum dots (QDs), have been applied in biomedical imaging in vitro and in vivo because of their fascinating optical properties. In this work, we investigated the application of CdTe QDs for tumor fluorescence in vivo imaging. Methods: The transparent dorsal skin fold window chamber (DSFC) was constructed on the 4~6 week-old BALB/c mice. The melanoma cells stably expressing green fluorescent protein ---ZsGreen were transplanted into the chamber and the melanoma DSFC model was established successfully. The water soluble CdTe QDs were synthesized and then administrated in the model through the tail intravenous injection. The fluorescent expression of B16 cells were assayed by fluorescent microscopy, the tumor growth, the blood capillaries distributions and its dynamic changes were observed by stereomicroscopy and laser scanning confocal microscopy. Results: The results demonstrated that the expression efficiency of ZsGreen was 41%, which met the experimental requirement. The tumors was visible inside the chamber after implantation of melanoma cells for 5~6 days, while no obvious changes in mice behaviors were found. After injection of the QDs, CdTe QDs accumulated at the invading edge of a range of solid tumor. We could also observe the tumor cells growth near the blood vessels, the angiogenesis occurred inside the tumor and the local blood capillaries increased. Conclusions: This work provided a new strategy for the tumor in vivo imaging and the development of targeted antineoplastic drugs.

  9. Inhibitory and Acceleratory Effects of Inonotus obliquus on Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Zheng-Fei Yan

    2014-01-01

    Full Text Available The aim of the present study is to preliminarily investigate the antimelanogenesis effect of Inonotus obliquus extracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered in Inonotus obliquus. In cells testing, betulin and trametenolic acid decreased tyrosinase activity and melanin content, while inotodiol and lanosterol significantly increased tyrosinase activity and melanin content, showing an AC⁡50 of 9.74 and 8.43 μM, respectively. Nicotinie acid, 3β,22,25-trihydroxy-lanosta-8-ene, had a little or no effect on tyrosinase. Betulin exhibited a mode of noncompetitive inhibition with a KI=KIS of 0.4 μM on tyrosinase activity showing an IC50 of 5.13 μM and being more effective than kojic acid (6.43 μM, and trametenolic acid exhibited a mode of mixed inhibition with a KI of 0.9 μM, KIS of 0.5 μM, and an IC50 of 7.25 μM. We proposed betulin and trametenolic acid as a new candidate of potent tyrosinase inhibitors and inotodiol and lanosterol as accelerators that could be used as therapeutic agent.

  10. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  11. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  12. Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer.

    Science.gov (United States)

    McEwan, Conor; Nesbitt, Heather; Nicholas, Dean; Kavanagh, Oisin N; McKenna, Kevin; Loan, Philip; Jack, Iain G; McHale, Anthony P; Callan, John F

    2016-07-01

    Sonodynamic therapy (SDT) involves the activation of a non-toxic sensitiser drug using low-intensity ultrasound to produce cytotoxic reactive oxygen species (ROS). Given the low tissue attenuation of ultrasound, SDT provides a significant benefit over the more established photodynamic therapy (PDT) as it enables activation of sensitisers at a greater depth within human tissue. In this manuscript, we compare the efficacy of aminolevulinic acid (ALA) mediated PDT and SDT in a squamous cell carcinoma (A431) cell line as well as the ability of these treatments to reduce the size of A431 ectopic tumours in mice. Similarly, the relative cytotoxic ability of Rose Bengal mediated PDT and SDT was investigated in a B16-melanoma cell line and also in a B16 ectopic tumour model. The results reveal no statistically significant difference in efficacy between ALA mediated PDT or SDT in the non-melanoma model while Rose Bengal mediated SDT was significantly more efficacious than PDT in the melanoma model. This difference in efficacy was, at least in part, attributed to the dark pigmentation of the melanoma cells that effectively filtered the excitation light preventing it from activating the sensitiser while the use of ultrasound circumvented this problem. These results suggest SDT may provide a better outcome than PDT when treating highly pigmented cancerous skin lesions. Copyright © 2016. Published by Elsevier Ltd.

  13. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  14. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    Directory of Open Access Journals (Sweden)

    Zanatta Daniela B

    2010-06-01

    Full Text Available Abstract Background Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods B16 (mouse melanoma and C6 (rat glioma cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet

  15. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  16. Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma

    International Nuclear Information System (INIS)

    Kobayashi, Masato; Nishii, Ryuichi; Shikano, Naoto; Flores, Leo G.; Mizutani, Asuka; Ogai, Kazuhiro; Sugama, Jyunko; Nagamachi, Shigeki; Kawai, Keiichi

    2015-01-01

    Introduction: A specific diagnosis for melanoma is strongly desired because malignant melanoma has poor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine ( 125 I-L-PC) was found to have good substrate affinity for tyrosinase enzyme in the melanin metabolic pathway, 123/131 I-L-PC had insufficient substrate affinity for tyrosinase to diagnose melanoma. In this study, we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4-hydroxyphenylcysteamine ( 125 I-PCA) to increase affinity for the melanin biosynthesis pathway. Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis. 125 I-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed biodistribution experiments using B16 melanoma-bearing mice using 125 I-PCA, 125 I-L-PC, 125 I-α-methyl-L-tyrosine, 123 I-m-iodobenzylguanidine and 67 Ga-citrate. In vitro assay was performed with B16 melanoma cells, and affinity for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabine and L-tyrosine inhibitor. In addition, partition coefficients of 125 I-PCA were evaluated. Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA was separated from 2-PCA at high purity. In biodistribution experiments, 125 I-PCA was accumulated and retained in B16 melanoma cells when compared with 125 I-L-PC. 125 I-PCA showed the highest values at 60 min after radiotracer injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of 125 I-PCA was significantly inhibited by phenylthiourea and thymidine. Partition coefficients of 125 I-PCA were lower than those of N-isopropyl-p-[ 123 I]iodoamphetamine and were not

  17. Acetylsalicylic acid inhibits the growth of melanoma tumors via SOX2-dependent-PAF-R-independent signaling pathway.

    Science.gov (United States)

    Thyagarajan, Anita; Saylae, Jeremiah; Sahu, Ravi P

    2017-07-25

    Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA. The current studies using stably PAF-R-positive (B16-PAFR) and negative (B16-MSCV) murine melanoma cells and PAF-R-expressing and deficient mice, demonstrate that ASA inhibits the in-vitro and in-vivo growth of highly aggressive B16F10 melanoma via bypassing tumoral or stromal PAF-R signaling. Similar ASA-induced effects in-vitro were seen in human melanoma and nasopharyngeal carcinoma cells positive or negative in PAF-R. Mechanistically, the ASA-induced decrease in cell survival and increase in apoptosis were significantly blocked by prostaglandin F2 alpha (PGF2α) agonists. Importantly, PCR array and qRT-PCR analysis of B16-tumors revealed significant downregulation of sry-related high-mobility-box-2 (SOX2) oncogene by ASA treatment. Interestingly, modulation of SOX2 expression by PGF2α agonists and upregulation by fibroblast growth factor 1 (FGF-1) rescued melanoma cells from ASA-induced decreased survival and increased apoptosis. Moreover, PGF2α-receptor antagonist, AL8810 mimics ASA-induced decreased melanoma cells survival which was significantly blocked by PGF2α and FGF-1. These findings indicate that ASA inhibits the growth of aggressive melanoma via SOX2-dependent-PAF-R-indepedent pathway.

  18. Stress indices for ANSI standard B16.11 socket-welding fittings

    International Nuclear Information System (INIS)

    Rodabaugh, E.C.; Moore, S.E.

    1975-08-01

    Stress indices for ANSI standard B16.11 socket-welding tees, 45 0 elbows, 90 0 elbows, and couplings are developed for intended use with the Class-1 piping system design rules of Section III--Division 1 of the ASME Boiler and Pressure Vessel Code. Indices are given for the evaluation of appropriate primary stresses, primary-plus-secondary stresses, and peak stresses due to internal pressure, bending-moment loads, and thermal gradients between the fitting and the attached pipe. The proposed indices are based on the dimensional and pressure-burst requirements of the B16.11 standard, the apparent shapes of B16.11 fittings as indicated from a random sampling taken off-the-shelf, the standard pressure-temperature ratings of the fittings, and on current stress indices now in the Code for similar butt-welding fittings. Specific recommendations are made for issuing the new stress indices in a Code case. (auth)

  19. Melanin content of hamster tissues, human tissues, and various melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  20. Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

    Directory of Open Access Journals (Sweden)

    Gismondi A

    2016-02-01

    Full Text Available Angelo Gismondi,1 Valentina Nanni,1 Giacomo Reina,2 Silvia Orlanducci,2 Maria Letizia Terranova,2 Antonella Canini1 1Department of Biology, 2Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome, Italy Abstract: For the first time, we coupled reduced detonation nanodiamonds (NDs with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin, and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy. Keywords: citropten, cytoskeletal structure, plant secondary metabolite, melanoma, internalization kinetics

  1. Norartocarpetin from a folk medicine Artocarpus communis plays a melanogenesis inhibitor without cytotoxicity in B16F10 cell and skin irritation in mice.

    Science.gov (United States)

    Ko, Horng-Huey; Tsai, Yi-Ting; Yen, Ming-Hong; Lin, Chun-Ching; Liang, Chan-Jung; Yang, Tsung-Han; Lee, Chiang-Wen; Yen, Feng-Lin

    2013-12-10

    Many natural products used in preventive medicine have also been developed as cosmeceutical ingredients in skin care products, such as Scutellaria baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant and antityrosinase activity compound in Artocarpus communis; however, the cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin have not been investigated yet. In the present study, cell viability in vitro and skin irritation in vivo are used to determine the safety of norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we examined the related-melanogenesis protein by western blot analysis for elucidating the antimelanogenesis mechanism of norartocarpin. The result of the present study demonstrated that norartocarpetin not only present non-cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in mice. Moreover, our result also first found that norartocarpetin downregulated phospho-cAMP response element-binding (phospho-CREB) and microphthalmia-associated transcription factor (MITF) expression, which in turn decreased both synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This process is dependent on norartocarpetin phosphorylation by mitogen-activated protein kinases such as phospho-JNK and phospho-p38, and it results in decreased melanogenesis. The present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study.

  2. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    Science.gov (United States)

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  3. 17 CFR 270.8b-16 - Amendments to registration statement.

    Science.gov (United States)

    2010-04-01

    ... company's investment objectives or policies (described in Item 8.2 of Form N-2) that have not been... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.8b-16 Amendments to registration statement. (a) Every registered management investment company which is required to file a semi-annual report...

  4. Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma

    Directory of Open Access Journals (Sweden)

    Primerano Donald A

    2008-10-01

    Full Text Available Abstract Background The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA. The molecular changes responsible for the biological activity of RA in melanoma are not well understood. Results In an analysis of sequential global gene expression changes during a 4–48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment between non-malignant melan-a mouse melanocytes and B16 melanoma cells. Using the same statistical test, we found 1495 genes whose expression was significantly higher in melan-a than in B16 cells and 2054 genes whose expression was significantly lower in melan-a than in B16 cells. By intersecting these two gene sets, we discovered a common set of 233 genes whose RNA levels were significantly different between B16 and melan-a cells and whose expression was altered by RA treatment. Within this set, RA treatment altered the expression of 203 (87% genes toward the melan-a expression level. In addition, hierarchical clustering showed that after 48 h of RA treatment expression of the 203 genes was more closely related to the melan-a gene set than any other RA treatment time point. Functional analysis of the 203 gene set indicated that RA decreased expression of mRNAs that encode proteins involved in cell division/cell cycle, DNA replication, recombination and repair, and transcription regulation. Conversely, it stimulated genes involved in cell-cell signaling, cell adhesion and cell differentiation/embryonic development. Pathway analysis of the 203 gene set revealed four major hubs of connectivity: CDC2, CHEK1, CDC45L and MCM6. Conclusion Our analysis of common genes in the 48 h RA-treatment of B16 melanoma cells and untreated B16

  5. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

    In this chapter, the author discusses various types of non-melanoma malignant skin cancer, as well as malignant melanoma. Non-melanoma skin cancer, such as basal cell and squamous cell carcinomas, occasionally metastasize, but only late in the course of the disease. On the other hand, even relatively small primary melanomas tend to disseminate to regional lymph nodes and to distant sites. The author presents various treatment plans, including radiation therapy. Cutaneous melanomas have been considered relatively radioresistant. This is the rationale for the use of large fraction radiation therapy in the treatment of melanomas with the fraction sizes varying from 4--8 Gy

  6. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    International Nuclear Information System (INIS)

    Ahmad, Israr; Muneer, Kashiff M.; Tamimi, Iman A.; Chang, Michelle E.; Ata, Muhammad O.; Yusuf, Nabiha

    2013-01-01

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome

  7. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Israr; Muneer, Kashiff M.; Tamimi, Iman A.; Chang, Michelle E.; Ata, Muhammad O. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Yusuf, Nabiha, E-mail: nabiha@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Veteran Affairs Medical Center, Birmingham, University of Alabama at Birmingham, AL (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, AL (United States)

    2013-07-01

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome.

  8. Treatment Option Overview (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  9. General Information about Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  10. Stages of Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  11. Melanoma - neck (image)

    Science.gov (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  12. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  13. Molecular Classification of Melanoma

    Science.gov (United States)

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  14. Melanoma International Foundation

    Science.gov (United States)

    ... the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use Toll-free: 866-463-6663 International: 610-942-3432 Melanoma International Foundation 250 Mapleflower ...

  15. [Ocular melanomas : An update].

    Science.gov (United States)

    Kalirai, H; Müller, P L; Jaehne, D; Coupland, S E

    2017-11-01

    Melanoma is the most common type of primary cancer to affect the adult eye. Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i. e. iris, ciliary body, and choroid), while the remaining 5% are located in the conjunctiva. Although both uveal and conjunctival melanomas are thought to derive from malignantly transformed melanocytes, uveal melanoma is clinically and biologically distinct from conjunctival melanoma, and indeed from its more common cutaneous counterpart. Intense efforts have been recently made to understand the molecular biology involved in the development of ocular melanomas, and in their progression. Molecular advances, particularly for uveal melanoma, have enhanced prognostication and the identification of rational therapeutic targets for disseminated disease. In this review, recent advances in the molecular characterisation of both uveal and conjunctival melanomas are discussed, and how these may be used to develop personalised therapeutic strategies.

  16. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  17. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  18. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  19. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2017-03-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  20. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  1. Mannosylerythritol lipid is a potent inducer of apoptosis and differentiation of mouse melanoma cells in culture.

    Science.gov (United States)

    Zhao, X; Wakamatsu, Y; Shibahara, M; Nomura, N; Geltinger, C; Nakahara, T; Murata, T; Yokoyama, K K

    1999-01-15

    Malignant melanomas are tumors that are well known to respond poorly to treatment with chemotherapeutic reagents. We report here that mannosylerythritol lipid (MEL), an extracellular glycolipid from yeast, markedly inhibited the growth of mouse melanoma B16 cells in a dose-dependent manner. Exposure of B16 cells to MEL at 10 microM and higher concentrations caused the condensation of chromatin, DNA fragmentation, and sub-G1 arrest, all of which are hallmarks of cells that are undergoing apoptosis. Analysis of the cell cycle also suggested that both the MEL-mediated inhibition of growth and apoptosis were closely associated with growth arrest in the G1 phase. Moreover, MEL exposure stimulated the expression of differentiation markers of melanoma cells, such as tyrosinase activity and the enhanced production of melanin, which is an indication that MEL triggered both apoptotic and cell differentiation programs. Forced expression of Bcl-2 protein in stably transformed B16 cells had a dual effect: it interfered with MEL-induced apoptosis but increased both tyrosinase activity and the production of melanin as compared with these phenomena in vector-transfected MEL-treated control B16 cells. These results provide the first evidence that growth arrest, apoptosis, and the differentiation of mouse malignant melanoma cells can be induced by a microbial extracellular glycolipid.

  2. Carbon ion induced DNA double-strand breaks in melanophore B16

    International Nuclear Information System (INIS)

    Wei Zengquan; Zhou Guangming; Wang Jufang; He Jing; Li Qiang; Li Wenjian; Xie Hongmei; Cai Xichen; Tao Huang; Dang Bingrong; Han Guangwu

    1997-01-01

    DNA double-strand breaks (DSBs) in melanophore B 16 induced by plateau and extended Bragg peak of 75 MeV/u 12 C 6+ ions were studied by using a technique of inverse pulsed-field gel electrophoresis (PIGE). DNA fragment lengths were distributed in two ranges: the larger in 1.4 Mbp-3.2 Mbp and the smaller in less than 1.2 Mbp. It indicates that distribution of DNA fragments induced by heavy ion irradiation is not stochastic and there probably are sensitive sites to heavy ions in DNA molecules of B 16 . Percentage of DNA released from plug (PR) increased and trended towards a quasi-plateau ∝85% as dose increased. Content of the larger fragments decreased and flattened with increasing dose while content of the smaller ones increased and trended towards saturation. (orig.)

  3. Uptake in melanoma cells of N-(2-diethylaminoethyl)-2-iodobenzamide (BZA2), an imaging agent for melanoma staging: relation to pigmentation.

    Science.gov (United States)

    Mansard, Sandrine; Papon, Janine; Moreau, Marie-France; Miot-Noirault, Elisabeth; Labarre, Pierre; Bayle, Martine; Veyre, Annie; Madelmont, Jean-Claude; Moins, Nicole

    2005-07-01

    N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)) has been singled out as the most efficacious melanoma scintigraphy imaging agent. Our work was designed to assess the mechanisms of the specific affinity of the radioiodinated iodobenzamide for melanoma tissue. We studied the cellular uptake and retention of [(125)I]-BZA(2) on various cell lines. In vitro, cellular [(125)I]-BZA(2) uptake was related to the pigmentation status of the cells: higher in pigmented melanoma cell lines (M4 Beu, IPC 227, B 16) than in a nonpigmented one (M3 Dau) and nonmelanoma cell lines (MCF 7 and L 929). Two mechanisms were assessed: binding of the tracer to melanin or to sigma receptors of melanoma cells. First, the uptake of [(125)I]-BZA(2) after melanogenesis stimulation by alpha-melanocyte-stimulating hormone and l-tyrosine increased in the B 16 melanoma cell line both in vitro and in vivo according to melanin concentration. Moreover, the binding of [(125)I]-BZA(2) to synthetic melanin was dependent on melanin concentration and could be saturated. Second, no competition was evidenced on M4 Beu cells between [(125)I]-BZA(2) and haloperidol, a sigma ligand, at concentrations < or =10(-6) M. We show that the specificity and sensibility of BZA(2) as a melanoma scintigraphic imaging agent are mostly due to interactions with melanic pigments.

  4. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  5. Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment

    Science.gov (United States)

    Chen, Xinhua; Swanson, R. James; Kolb, Juergen F.; Nuccitelli, Richard; Schoenbach, Karl H.

    2011-01-01

    Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (Pelectric fields surrounding the needle electrodes. PMID:19730404

  6. Tumor progression in uveal melanoma

    NARCIS (Netherlands)

    C.M. Mooij (Cornelia)

    1995-01-01

    textabstractOphthalmic melanomas can be divided in extra-ocular (conjunctiva, caruncle) and intraocular uveal melanomas (iris, ciliary body and choroid). Uveal melanomas account for 95% of ocular melanomas, while only 5% are conjunctival in origin. The extra-ocular and intra-ocular melanomas differ

  7. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies

    International Nuclear Information System (INIS)

    Pozzi, Oscar R.; Edreira, Martin M.; Castiglia, Silvia G.; Soroa, Victoria E.

    1999-01-01

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[ 131 I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

  8. Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

  9. Antrodia camphorata Grown on Germinated Brown Rice Suppresses Melanoma Cell Proliferation by Inducing Apoptosis and Cell Differentiation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Minjung Song

    2013-01-01

    Full Text Available Antrodia camphorata grown on germinated brown rice (CBR was prepared to suppress melanoma development. CBR extracts were divided into hexane, EtOAc, BuOH, and water fractions. Among all the fractions, EtOAc fraction showed the best suppressive effect on B16F10 melanoma cell proliferation by CCK-8 assay. It also showed the increased cell death and the changed cellular morphology after CBR treatment. Annexin V-FITC/PI, flow cytometry, and western blotting were performed to elucidate anticancer activity of CBR. The results showed that CBR induced p53-mediated apoptotic cell death of B16F10. CBR EtOAc treatment increased melanin content and melanogenesis-related proteins of MITF and TRP-1 expressions, which supports its anticancer activity. Its potential as an anticancer agent was further investigated in tumor-xenografted mouse model. In melanoma-xenografted mouse model, melanoma tumor growth was significantly suppressed under CBR EtOAc fraction treatment. HPLC analysis of CBR extract showed peak of adenosine. In conclusion, CBR extracts notably inhibited B16F10 melanoma cell proliferation through the p53-mediated apoptosis induction and increased melanogenesis. These findings suggest that CBR EtOAc fraction can act as an effective anticancer agent to treat melanoma.

  10. Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis.

    Science.gov (United States)

    Zhou, Ping; Qin, Jiaqi; Li, Yuan; Li, Guoxia; Wang, Yinsong; Zhang, Ning; Chen, Peng; Li, Chunyu

    2017-09-02

    Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened activations of protein kinase C ζ (PKCζ) and cyclooxygenase-2 (COX-2) signaling pathways. Targeted inhibitions for PKCζ and COX-2 have been considered as the promising strategies for the treatment of melanoma metastasis. Thus, the PKCζ inhibitor J-4 and COX-2 inhibitor Celecoxib were combined to treat melanoma metastasis in this study. The Transwell assay, Wound-healing assay and Adhesion assay were used to evaluate the inhibition of combined therapy of J-4 and Celecoxib on melanoma cells invasion, migration and adhesion in vitro, respectively. The impaired actin polymerization was observed by confocal microscope and inactivated signal pathways about PKCζ and COX-2 were confirmed by the Western blotting assay. The B16-F10/C57BL mouse melanoma model was used to test the inhibition of combined therapy of J-4 and Celecoxib on melanoma metastasis in vivo. The in vitro results showed that the combination of J-4 and Celecoxib exerted synergistic inhibitory effects on the migration, invasion and adhesion of melanoma B16-F10 and A375 cells with combination index less than 1. The actin polymerization and phosphorylation of Cofilin required in cell migration were severely impaired, which is due to the inactivation of PKCζ related signal pathways and the decrease of COX-2. The combined inhibition of PKCζ and COX-2 induced Mesenchymal-Epithelial Transition (MET) in melanoma cells with the expression of E-Cadherin increasing and Vimentin decreasing. The secretion of MMP-2/MMP-9 also significantly decreased after the combination treatment. In C57BL/6 mice intravenously injected with B16-F10 cells (5 × 10 4 cells/mouse), co-treatment of J-4 and Celecoxib also severely suppressed melanoma lung metastasis. The body weight monitoring and HE staining results indicated the

  11. Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor GrowthIn vivoUsing Mechanistic Models and Simulation.

    Science.gov (United States)

    Klinke, David J; Wang, Qing

    2016-01-01

    A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model.

  12. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    Science.gov (United States)

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  13. Biochemical mechanism of acetylsalicylic acid (Aspirin) selective toxicity toward melanoma cell lines.

    Science.gov (United States)

    Vad, Nikhil M; Yount, Garret; Moridani, Majid Y

    2008-12-01

    In the current work, we investigated the biochemical toxicity of acetylsalicylic acid (ASA; Aspirin) in human melanoma cell lines using tyrosinase enzyme as a molecular cancer therapeutic target. At 2 h, ASA was oxidized 88% by tyrosinase. Ascorbic acid and NADH, quinone reducing agents, were significantly depleted during the enzymatic oxidation of ASA by tyrosinase to quinone. The 50% inhibitory concentration (48 h) of ASA and salicylic acid toward SK-MEL-28 cells were 100 micromol/l and 5.2 mmol/l, respectively. ASA at 100 micromol/l was selectively toxic toward human melanocytic SK-MEL-28, MeWo, and SK-MEL-5 and murine melanocytic B16-F0 and B16-F10 melanoma cell lines. However, ASA was not significantly toxic to human amelanotic C32 melanoma cell line, which does not express tyrosinase enzyme, and human nonmelanoma BJ, SW-620, Saos, and PC-3 cells. Dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased ASA toxicity toward SK-MEL-28 cells indicating quinone formation and intracellular GSH depletion played important mechanistic roles in ASA-induced melanoma toxicity. Ascorbic acid, a quinone reducing agent, and GSH, an antioxidant and quinone trap substrate, prevented ASA cell toxicity. Trifluoperazine, inhibitor of permeability transition pore in mitochondria, prevented ASA toxicity. ASA led to significant intracellular GSH depletion in melanocytic SK-MEL-28 melanoma cells but not in amelanotic C32 melanoma cells. ASA also led to significant reactive oxygen species (ROS) formation in melanocytic SK-MEL-28 melanoma cells but not in amelanotic C32 melanoma cells. ROS formation was exacerbated by dicoumarol and 1-bromoheptane in SK-MEL-28. Our investigation suggests that quinone species, intracellular GSH depletion, ROS formation, and mitochondrial toxicity significantly contributed toward ASA selective toxicity in melanocytic SK-MEL-28 melanoma cells.

  14. Kidney Transplant

    Science.gov (United States)

    ... Menu Menu Search Home Prevention Kidney Disease Patients Organ Donation & Transplantation Professionals Events Advocacy Donate A to Z Health ... Tests for Transplant Care After Kidney Transplant Common Organ Donation and Transplantation Terms The National Kidney Foundation (NKF) is the ...

  15. Novel (1E,3E,5E-1,6-bis(Substituted phenylhexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish

    Directory of Open Access Journals (Sweden)

    Jisun Oh

    2018-04-01

    Full Text Available The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E-1,6-bis(substituted phenylhexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TYRP1, and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

  16. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  17. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  18. Annexin A1 in primary tumors promotes melanoma dissemination.

    Science.gov (United States)

    Boudhraa, Zied; Rondepierre, Fabien; Ouchchane, Lemlih; Kintossou, Roselyne; Trzeciakiewicz, Anna; Franck, Frederic; Kanitakis, Jean; Labeille, Bruno; Joubert-Zakeyh, Juliette; Bouchon, Bernadette; Perrot, Jean Luc; Mansard, Sandrine; Papon, Janine; Dechelotte, Pierre; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Bonnet, Mathilde; D'Incan, Michel; Degoul, Françoise

    2014-10-01

    Metastatic melanoma is one of the most aggressive forms of skin cancer and has a poor prognosis. We have previously identified Annexin A1 (ANXA1) as a potential murine melanoma-spreading factor that may modulate cell invasion by binding to formyl peptide receptors (FPRs). Here, we report that (1) in a B16Bl6 spontaneous metastasis model, a siRNA-induced decrease in tumoral ANXA1 expression significantly reduced tumoral MMP2 activity and number of lung metastases; (2) in a retrospective study of 61 patients, metastasis-free survival was inversely related to ANXA1 expression levels in primary tumors (HR 3.15 [1.03-9.69], p = 0.045); (3) in human melanoma cell lines, ANXA1 level was positively correlated with in vitro invasion capacity whereas normal melanocytes contained low ANXA1 levels, and (4) the ANXA1 N-terminal peptide ANXA12-26 stimulated MMP2 activity after interaction with FPRs and significantly stimulated the in vitro invasion of melanomas by acting on FPRs. These findings identify ANXA1 as a proinvasive protein in melanoma that holds promise as a potential prognostic marker and therapeutic target.

  19. The modulation of Dicer regulates tumor immunogenicity in melanoma.

    Science.gov (United States)

    Hoffend, Nicholas C; Magner, William J; Tomasi, Thomas B

    2016-07-26

    MicroRNAs (miRs) are small non-coding RNAs that regulate most cellular protein networks by targeting mRNAs for translational inhibition or degradation. Dicer, a type III endoribonuclease, is a critical component in microRNA biogenesis and is required for mature microRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. For example, increased Dicer expression in melanoma is associated with more aggressive tumors (higher tumor mitotic index and depth of invasion) and poor patient prognosis. However, the role that Dicer plays in melanoma development and immune evasion remains unclear. Here, we report on a newly discovered relationship between Dicer expression and tumor immunogenicity. To investigate Dicer's role in regulating melanoma immunogenicity, Dicer knockdown studies were performed. We found that B16F0-Dicer deficient cells exhibited decreased tumor growth compared to control cells and were capable of inducing anti-tumor immunity. The decrease in tumor growth was abrogated in immunodeficient NSG mice and was shown to be dependent upon CD8+ T cells. Dicer knockdown also induced a more responsive immune gene profile in melanoma cells. Further studies demonstrated that CD8+ T cells preferentially killed Dicer knockdown tumor cells compared to control cells. Taken together, we present evidence which links Dicer expression to tumor immunogenicity in melanoma.

  20. CASE REPORT: NODULAR MELANOMA

    Directory of Open Access Journals (Sweden)

    Tina Zupančič

    2015-05-01

    Full Text Available Nodular melanoma is a rare type of cutaneous melanoma with an increased risk of death. It often mimics benign cutaneous tumors and inflammatory lesions. It has pronounced vertical growth phase and greater thickness at the time of diagnosis which caries ominous prognostic value. Nodular melanoma quickly develops metastases which are often present before the disease is clinically recognised. Here, we report a case of nodular melanoma clinically mimicking seborrheic keratosis. Therapy and 36 months follow-up after primal excision are also presented.

  1. The chick embryo as an experimental system for melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Christian Busch

    Full Text Available BACKGROUND: A primary cutaneous melanoma will not kill the patient, but its metastases. Since in vitro studies on melanoma cells in 2-D cultures do often not reflect reality, 3-D models might come closer to the physiological situation in the patient during cancer initiation and progression. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe the chick embryo model for in vivo studies of melanoma cell migration and invasion. After transplantation of neural crest-derived melanoma cells into the neural tube, the melanoma cells resume neural crest cell migration along the medial and lateral pathways and finally undergo apoptosis in the target areas. Upon transplantation into ectopic areas such as the hindbrain or the optic cup malignant invasion and local tissue destruction occurs. In contrast, melanocytes are not able to spontaneously resume neural crest cell migration. However, malignant invasion can be induced in melanocytes by pre-treatment with the TGF-beta family members bone morphegenetic protein-2 or nodal. Transplantation of MCF7 breast cancer cells yields a different growth pattern in the rhombencephalon than melanoma cells. CONCLUSIONS/SIGNIFICANCE: The chick embryo model is a feasible, cost-effective in vivo system to study invasion by cancer cells in an embryonic environment. It may be useful to study invasive behavior induced by embryonic oncogenes and for targeted manipulation of melanoma or breast cancer cells aiming at ablation of invasive properties.

  2. Melanoma Therapy via Peptide-Targeted a-Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Hylarides, Mark; Fisher, Darrell R.; Shelton, Tiffani; Moore, Herbert A.; Wester, Dennis W.; Fritzberg, Alan R.; Winkelmann, Christopher T.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-08-01

    Malignant melanoma is the most lethal form of skin cancer. Current chemotherapy and external beam radiation therapy regimens are ineffective agents against melanoma, as shown by a 10-year survival rate for patients with disseminated disease of approximately 5% (reference?). In this study, the unique combination of a melanoma targeting peptide and an in vivo generated a-particle emitting radioisotope was investigated for its melanoma therapy potential. Alpha-radiation is densely ionizing and energy is locally absorbed, resulting in high concentrations of destructive free radicals and irreparable DNA double strand breaks. This high linear-energy-transfer overcomes radiation resistant tumor cells and oxygen-enhancement effects. The melanoma targeting peptide DOTA-Re(Arg11)CCMSH was radiolabeled with 212Pb, the parent of 212Bi, which decays via alpha and beta decay. Biodistribution and therapy studies were performed in the B16/F1 melanoma bearing C57 mouse flank tumor model. 212Pb[DOTA]-R e(Arg11)CCMSH exhibited rapid tumor uptake and extended retention coupled with rapid whole body disappearance. Radiation dose delivered to the tumor was estimated to be 61 cGy/uCi 212Pb administered. Treatment of melanoma-bearing mice with 50, 100 and 200 uCi of 212Pb[DOTA]-Re(Arg11)CCMSH extended mean survival of mice to 22, 28, and 49.8 days, respectively, compared to the 14.6 day mean survival of the placebo control group. Forty-five percent of the mice receiving 200 uCi survived the study disease-free.

  3. Comparative study of angio genesis radiopharmaceuticals for melanoma detection

    International Nuclear Information System (INIS)

    Oliveira, Erica Aparecida de

    2011-01-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99m Tc-MAG3-PEG 8 -c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99m Tc-MAG 3 -PEG 8 -c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  4. Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

    International Nuclear Information System (INIS)

    Nie, Yunzhong; Du, Leilei; Mou, Yongbin; Xu, Zhenjun; Weng, Leihua; Du, Youwei; Zhu, Yanan; Hou, Yayi; Wang, Tingting

    2013-01-01

    We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function. The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 10 5 B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured. The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased. LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma

  5. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  6. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  7. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  8. Uveal melanoma: estimating prognosis.

    Science.gov (United States)

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  9. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  10. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  11. Melanoma do aparelho ungueal Nail apparatus melanoma

    Directory of Open Access Journals (Sweden)

    Ignez Regina dos Santos Muri Mendonça

    2004-10-01

    Full Text Available O melanoma do aparelho ungueal é apresentação relativamente rara dessa neoplasia, muitas vezes diagnosticada como nevo juncional, hematoma subungueal ou mesmo onicomicose. Esse fato leva a um atraso no diagnóstico e, conseqüentemente, na instituição da terapêutica específica, contribuindo para agravar o prognóstico de uma doença que por si só já é muito agressiva. Os autores relatam um caso de melanoma no primeiro quirodáctilo esquerdo de uma paciente negra com evolução de um ano, ressaltando a importância de avaliar certos critérios clínicos para obter o diagnóstico em fases mais precoces da doença.Nail apparatus melanoma is a rare presentation of melanoma and may be misdiagnosed as junctional nevus, subungual hematoma or onychomycosis. This fact often leads initially to inappropriate treatment and significant delays in appropriately managing such an aggressive disease. The authors report a case of melanoma on the left thumb of a black patient evolving for a year. Emphasis was placed on the importance of assessing certain clinical characteristics in order to reach an early diagnosis.

  12. Melanoma during pregnancy

    DEFF Research Database (Denmark)

    de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

    2017-01-01

    The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

  13. Photodynamic therapy of melanoma skin cancer using carbon dot - chlorin e6 - hyaluronate conjugate.

    Science.gov (United States)

    Beack, Songeun; Kong, Won Ho; Jung, Ho Sang; Do, In Hwan; Han, Seulgi; Kim, Hyemin; Kim, Ki Su; Yun, Seok Hyun; Hahn, Sei Kwang

    2015-10-01

    Despite wide application of photodynamic therapy (PDT) for the treatment of melanoma skin cancers, there are strong biomedical unmet needs for the effective generation of singlet oxygen after targeted delivery of photosensitizers. Here, we investigated a facile PDT of melanoma skin cancer using transdermal carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. The Cdot-Ce6-HA conjugate was synthesized by the coupling reaction of diaminohexane modified HA (DAH-HA) with the carboxylic group of Ce6. The singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. The enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice were corroborated by confocal microscopy and two-photon microscopy. The laser irradiation after topical treatment with Cdot-Ce6-HA conjugates resulted in complete suppression of melanoma skin cancers. The antitumor effect was confirmed by histological analysis with H&E staining and TUNEL assay for tumor apoptosis. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers. To our knowledge, this is the first report on a facile transdermal photodynamic therapy (PDT) of melanoma skin cancer using carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. We found that the singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. Confocal microscopy and two-photon microscopy clearly confirmed the enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers. Copyright © 2015 Acta Materialia Inc. All rights reserved.

  14. Cutaneous manifestations associated with melanoma.

    Science.gov (United States)

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Improvement of AdCMV-GFP gene transfection efficiency induced by heavy-ion beam irradiation on murine melanoma cells

    International Nuclear Information System (INIS)

    Duan Xin; Min Fengling; Liu Bing; Zhou Qingming; Li Xiaoda; Wang Yanling; Chinese Academy of Sciences, Beijing; Zhang Hong; Qiu Rong; Hao Jifang; Zhou Guangming; Gao Qingxiang

    2007-01-01

    The effect of 12 C 6+ beam irradiation on AdCMV-GFP (a replication deficient recombinant adenoviral vector containing CMV promoter and green fluorescent protein) gene transfection efficiency for murine melanoma cell B16 has been investigated. B16 cells infected with AdCMV-GFP were irradiated by different doses of 12 C 6+ beam. The transfection efficiency was assessed by flow cytometry (FCM). Results show that 12 C 6+ beam irradiation can improve transfection efficiency of AdCMV-GFP on murine melanoma cell B16 in a dose-dependent manner. In addition, the transfection efficiency in pre-tranfection plus irradiation group is higher than that in pre-irradiation plus transfection group at the same dose irradiation dose. (authors)

  16. Single Photon Emission Computed Tomography/Positron Emission Tomography Imaging and Targeted Radionuclide Therapy of Melanoma: New Multimodal Fluorinated and Iodinated Radiotracers

    International Nuclear Information System (INIS)

    Maisonial, A.; Papon, J.; Bayle, M.; Vidal, A.; Auzeloux, Ph.; Rbah, L.; Bonnet-Duquennoy, M.; Miot-Noirault, E.; Galmier, M.J.; Borel, M.; Madelmont, J.C.; Moins, N.; Chezal, J.M.; Kuhnast, B.; Boisgard, R.; Dolle, F.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Askienazy, S.

    2011-01-01

    This study reports a series of 14 new iodinated and fluorinated compounds offering both early imaging ( 123 I, 124 I, 18 F) and systemic treatment ( 131 I) of melanoma potentialities. The biodistribution of each 125 I-labeled tracer was evaluated in a model of melanoma B16F0-bearing mice, using in vivo serial γ scintigraphic imaging. Among this series, [ 125 I]56 emerged as the most promising compound in terms of specific tumoral uptake and in vivo kinetic profile. To validate our multimodality concept, the radiosynthesis of [ 18 F]56 was then optimized and this radiotracer has been successfully investigated for in vivo PET imaging of melanoma in B16F0- and B16F10-bearing mouse model. The therapeutic efficacy of [ 131 I]56 was then evaluated in mice bearing subcutaneous B16F0 melanoma, and a significant slow down in tumoral growth was demonstrated. These data support further development of 56 for PET imaging ( 18 F, 124 I) and targeted radionuclide therapy ( 131 I) of melanoma using a single chemical structure. (authors)

  17. Expression and functions of galectin-7 in human and murine melanomas.

    Directory of Open Access Journals (Sweden)

    Katherine Biron-Pain

    Full Text Available The identification of galectin-7 as a p53-induced gene and its ability to induce apoptosis in many cell types support the hypothesis that galectin-7 has strong antitumor activity. This has been well documented in colon cancer. However, in some cases, such as breast cancer and lymphoma, its high expression level correlates with aggressive subtypes of cancer, suggesting that galectin-7 may have a dual role in cancer progression. In fact, in breast cancer, overexpression of galectin-7 alone is sufficient to promote metastasis to the bone and lung. In the present work, we investigated the expression and function of galectin-7 in melanoma. An analysis of datasets obtained from whole-genome profiling of human melanoma tissues revealed that galectin-7 mRNA was detected in more than 90% of biopsies of patients with nevi while its expression was more rarely found in biopsies collected from patients with malignant melanoma. This frequency, however, was likely due to the presence of normal epidermis tissues in biopsies, as shown our studies at the protein level by immunohistochemical analysis. Using the experimental melanoma B16F1 cell line, we found that melanoma cells can express galectin-7 at the primary tumor site and in lung metastasis. Moreover, we found that overexpression of galectin-7 increased the resistance of melanoma cells to apoptosis while inducing de novo egr-1 expression. Overexpression of galectin-7, however, was insufficient to modulate the growth of tumors induced by the subcutaneous injection of B16F1 cells. It also failed to modulate the dissemination of B16F1 cells to the lung.

  18. Cell Surface Heparan Sulfate Released by Heparanase Promotes Melanoma Cell Migration and Angiogenesis

    Science.gov (United States)

    Roy, Madhuchhanda; Marchetti, Dario

    2009-01-01

    Heparan sulfate proteoglycans are essential components of the cell-surface and extracellular matrix which provide structural integrity and act as storage depots for growth factors and chemokines, through their heparan sulfate (HS) side chains. Heparanase is the only mammalian endoglycosidase known that cleaves HS, thus contributing to matrix degradation and cell invasion. The enzyme acts as an endo-β-D-glucuronidase resulting in HS fragments of discrete molecular weight size. Cell-surface HS is known to inhibit or stimulate tumorigenesis depending upon size and composition. We hypothesized that heparanase contributes to melanoma metastasis by generating bioactive HS from the cell-surface to facilitate biological activities of tumor cells as well as tumor microenvironment. We removed cell-surface HS from melanoma (B16B15b) by HPSE treatment and resulting fragments were isolated. Purified cell-surface HS stimulated in vitro B16B15b cell migration but not proliferation, and importantly, enhanced in vivo angiogenesis. Furthermore, melanoma cell-surface HS did not affect in vitro endothelioma cell (b.End3) migration. Our results provide direct evidence that, in addition to remodeling extracellular matrix and releasing growth factors and chemokines, HPSE contributes to aggressive phenotype of melanoma by releasing bioactive cell-surface HS fragments which can stimulate melanoma cell migration in vitro and angiogenesis in vivo. PMID:19115257

  19. The in-vitro and in-vivo inhibitory activity of biflorin in melanoma.

    Science.gov (United States)

    Vasconcellos, Marne C; Bezerra, Daniel P; Fonseca, Aluísio M; Araújo, Ana Jérsia; Pessoa, Cláudia; Lemos, Telma L G; Costa-Lotufo, Letícia V; de Moraes, Manoel Odorico; Montenegro, Raquel C

    2011-04-01

    Biflorin, an ortho-naphthoquinone, is an active compound found in the roots of Capraria biflora L. It has been reported that biflorin presents anticancer activity, inhibiting both tumor cell line growth in culture and tumor development in mice. The aim of this study was to examine the effectiveness of biflorin treatment using both in-vitro and in-vivo melanoma models. Biflorin displayed considerable cytotoxicity against all tested cell lines, with half maximal inhibitory concentration values ranging from 0.58 μg/ml in NCI H23 (human lung adenocarcinoma) to 14.61 μg/ml in MDA-MB-231 (human breast cancer) cell lines. In a second set of experiments using B16 melanoma cells as a model, biflorin reduced cell viability but did not cause significant increase in the number of nonviable cells. In addition, the DNA synthesis was significantly inhibited. Flow cytometry analysis showed that biflorin may lead to an apoptotic death in melanoma cells, inducing DNA fragmentation and mitochondria depolarization, without affecting membrane integrity. In B16 melanoma-bearing mice, administration of biflorin (25mg/day) for 10 days inhibited tumor growth, and also increased the mean survival rate from 33.3±0.9 days (control) to 44.5±3.4 days (treated). Our findings suggest that biflorin may be considered as a promising lead compound for designing new drugs to be used in the treatment of melanoma.

  20. Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

    Science.gov (United States)

    Lonsdorf, Anke S.; Krämer, Björn F.; Fahrleitner, Manuela; Schönberger, Tanja; Gnerlich, Stephan; Ring, Sabine; Gehring, Sarah; Schneider, Stefan W.; Kruhlak, Michael J.; Meuth, Sven G.; Nieswandt, Bernhard; Gawaz, Meinrad; Enk, Alexander H.; Langer, Harald F.

    2012-01-01

    A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothelium in vitro under shear conditions. Constitutively active platelet receptor GPIIb/IIIa (integrin αIIbβ3) expressed on Chinese hamster ovary cells promoted melanoma cell adhesion in the presence of fibrinogen, whereas blocking antibodies to aνβ3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion to platelets. Furthermore, using intravital microscopy, we observed functional platelet-melanoma cell interactions, as platelet depletion resulted in significantly reduced melanoma cell adhesion to the injured vascular wall in vivo. Using a mouse model of hematogenous metastasis to the lung, we observed decreased metastasis of B16 melanoma cells to the lung by treatment with a mAb blocking the aν subunit of aνβ3 integrin. This effect was significantly reduced when platelets were depleted in vivo. Thus, the engagement of GPIIb/IIIa with aνβ3 integrin interaction mediates tumor cell-platelet interactions and highlights how this interaction is involved in hematogenous tumor metastasis. PMID:22102277

  1. In vivo UVA irradiation of mouse is more efficient in promoting pulmonary melanoma metastasis than in vitro

    Directory of Open Access Journals (Sweden)

    Ylianttila Lasse

    2011-06-01

    Full Text Available Abstract Background We have previously shown in vitro that UVA increases the adhesiveness of mouse B16-F1 melanoma cells to endothelium. We have also shown in vivo that UVA exposure of C57BL/6 mice, i.v. injected with B16-F1 cells, increases formation of pulmonary colonies of melanoma. The aim of the present animal study was to confirm the previously observed in vivo UVA effect and to determine whether in vitro UVA-exposure of melanoma cells, prior the i.v. injection, will have an enhancing effect on the pulmonary colonization capacity of melanoma cells. As a second aim, UVA-derived immunosuppression was determined. Methods Mice were i.v. injected with B16-F1 cells into the tail vein and then immediately exposed to UVA. Alternatively, to study the effect of UVA-induced adhesiveness on the colonization capacity of B16-F1 melanoma, cells were in vitro exposed prior to i.v. injection. Fourteen days after injection, lungs were collected and the number of pulmonary nodules was determined under dissecting microscope. The UVA-derived immunosuppression was measured by standard contact hypersensitivity assay. Results and Discussion Obtained results have confirmed that mice, i.v. injected with B16-F1 cells and thereafter exposed to UVA, developed 4-times more of melanoma colonies in lungs as compared with the UVA non-exposed group (p in vitro exposure of melanoma cells prior to their injection into mice, led only to induction of 1.5-times more of pulmonary tumor nodules, being however a statistically non-significant change. The obtained results postulate that the UVA-induced changes in the adhesive properties of melanoma cells do not alone account for the 4-fold increase in the pulmonary tumor formation. Instead, it suggests that some systemic effect in a mouse might be responsible for the increased metastasis formation. Indeed, UVA was found to induce moderate systemic immunosuppression, which effect might contribute to the UVA-induced melanoma

  2. Influence of rosmarinic acid and Salvia officinalis extracts on melanogenesis of B16F10 cells

    Directory of Open Access Journals (Sweden)

    Karina B. Oliveira

    2013-04-01

    Full Text Available Melanin is a photoprotective skin pigment, and pathologies characterized by hypo or hyperpigmentation are common. New compounds that regulate melanogenesis are, therefore, opportune, and many natural products with this property, as polyphenols, have been described. Salvia officinalis L., Lamiaceae, is a widely used food spice that contains high amounts of phenol derivates, including rosmarinic acid. The aim of this work was to evaluate the contribution of rosmarinic acid in the melanogenic activity of sage extracts. Fluid and aqueous extracts of sage and purified rosmarinic acid were assayed for B16F10 cytotoxicity and, then, evaluated on melanin production and tyrosinase activity. While sage extracts showed a concentration-dependent ability to significantly increase melanin production without necessarily changing the enzymatic activity, rosmarinic acid showed a dual behavior on melanogenesis, increasing melanin biosynthesis and tyrosinase activity at low concentrations and decreasing it at higher levels. Rosmarinic acid may collaborate with sage extracts activity on melanogenesis, although other compounds may be involved. This is the first time that a dual action of rosmarinic acid on melanogenesis is reported, which may be useful in further studies for therapeutic formulations to treat skin pigmentation disorders.

  3. Efektivitas kurkumin sebagai antioksidan dan inhibitor melanin pada kultur sel B16F1

    Directory of Open Access Journals (Sweden)

    Sugiharto Sugiharto

    2013-03-01

    Full Text Available Melanin inhibitors have become increasingly important ingredients in medication and cosmetics for the prevention ofhyperpigmentation. In the last few years, a huge number of natural herbal extracts have been tested as inhibitors of melanin synthesisand some of these effects are related to the antioxidant properties. The objectives of this study were to determine of curcumin propertiesas antioxidant activity and melanin inhibitors. In this study, our data indicated that antioxidant assay with DPPH showed IC50 was16,05 μg/ml. In the absence of α-MSH (α-Melanocyte Stimulating Hormone, melanin content assay in cell B16-F1 indicated thatthe highest activity of curcumin to reduce melanin content of 45,67% at 25 μg/ml. Meanwhile, in the presence of α-MSH at the sameconcentration indicated that the highest activity was 53,87%. Based on the data, curcumin has potential properties as antioxidantactivity and melanin inhibitor.

  4. Influence of rosmarinic acid and Salvia officinalis extracts on melanogenesis of B16F10 cells

    Directory of Open Access Journals (Sweden)

    Karina B. Oliveira

    2012-11-01

    Full Text Available Melanin is a photoprotective skin pigment, and pathologies characterized by hypo or hyperpigmentation are common. New compounds that regulate melanogenesis are, therefore, opportune, and many natural products with this property, as polyphenols, have been described. Salvia officinalis L., Lamiaceae, is a widely used food spice that contains high amounts of phenol derivates, including rosmarinic acid. The aim of this work was to evaluate the contribution of rosmarinic acid in the melanogenic activity of sage extracts. Fluid and aqueous extracts of sage and purified rosmarinic acid were assayed for B16F10 cytotoxicity and, then, evaluated on melanin production and tyrosinase activity. While sage extracts showed a concentration-dependent ability to significantly increase melanin production without necessarily changing the enzymatic activity, rosmarinic acid showed a dual behavior on melanogenesis, increasing melanin biosynthesis and tyrosinase activity at low concentrations and decreasing it at higher levels. Rosmarinic acid may collaborate with sage extracts activity on melanogenesis, although other compounds may be involved. This is the first time that a dual action of rosmarinic acid on melanogenesis is reported, which may be useful in further studies for therapeutic formulations to treat skin pigmentation disorders.

  5. Kidney Transplant

    Science.gov (United States)

    ... type matches or is compatible to your own. Blood-type incompatible transplants are also possible but require additional medical treatment before and after transplant to reduce the risk of organ rejection. These are known as ABO incompatible kidney transplants. ...

  6. Kidney transplant

    Science.gov (United States)

    ... place a healthy kidney into a person with kidney failure . ... Renal transplant; Transplant - kidney ... Becker Y, Witkowski P. Kidney and pancreas transplantation. In: Townsend CM ... Urology . 11th ed. Philadelphia, PA: Elsevier; 2016: ...

  7. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  8. Management of Melanoma Families

    Directory of Open Access Journals (Sweden)

    Wilma Bergman

    2010-04-01

    Full Text Available In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1 management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2 variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3 background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.

  9. Post-transplantation Malignancy After Kidney Transplantation in Turkey.

    Science.gov (United States)

    Keles, Y; Tekin, S; Duzenli, M; Yuksel, Y; Yücetin, L; Dosemeci, L; Sengul, A; Demirbaş, A; Tuncer, M

    2015-06-01

    Kidney transplantation is the best treatment option for end-stage renal disease patients. Increased incidence of post-transplantation malignancy can be caused by immunosuppressive drugs and some oncogenic infections. The aim of this study is to show the incidence of post-transplantation malignancy in patients who had surgery and were followed up in the Organ Transplant Center, Medical Park Antalya, Antalya, Turkey. The study was based on 2100 kidney transplantation patients who had surgery between May 2008 and December 2012 and also on 1900 patients who had surgery by members of our team in other centers and who were followed up routinely. In all of our patients, the type of malignancy, the time that malignancy developed, immunosuppressive regimens, and viral status (Epstein-Barr virus and cytomegalovirus) were investigated. Malignancy was developed in 30 patients (60% of them were male, median age was 52.1 years). Post-transplantation malignancy development time was a median of 5.1 years. The types of malignancies were as follows: non-melanoma skin cancer in 12 patients (40%), urogenital cancer in 7 patients (24%), breast cancer in 4 patients (14%), lymphoproliferative disease in 3 patients (10%), thyroid cancer in 2 patients (6%), and lung cancer in 2 patients (6%). In this study, we did not find any increased post-transplantation malignancy risk in our patients. This finding could be due to the low-dosage immunosuppressive protocols that we used. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    Science.gov (United States)

    2017-06-05

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  11. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  12. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive......-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  13. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  14. Primary leptomeningeal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Aichner, F.; Schuler, G.

    1982-11-01

    A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue (''leptomeningeal melanomatosis''), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

  15. Magnetic and thermal behaviour of the amorphous ferromagnet Fe79B16Si5

    International Nuclear Information System (INIS)

    Shaisha, E.E.; Bahgat, A.A.

    1985-01-01

    Spin waves in the amorphous ferromagnet Fe 79 B 16 Si 5 are studied by Moessbauer effect spectroscopy. The magnetic hyperfine field (MHF) is measured at the Fe sites of such a ferromagnet, which exhibits a temperature dependence of the form, H(T)/H(0) = (1 - BT/sup 3/2/ - CT/sup 5/2/), indicative of spin wave excitations in amorphous ferromagnets. The T/sup 3/2/ behaviour and the distribution of the exchange interactions are studied in detail as a function of the MHF. The spin wave excitations constant B/sub 3/2/ = BT/sub C//sup 3/2/ = 0.3 +- 0.05 and C/sub 5/2/ = CT/sub C//sup 5/2/ = 0.3 +- 0.05,Are obtained by fitting the experimental data, and where T/sub C/ = 670 K. The results sh=ow that the contribution of C/sub 5/2/ is extremely effective above 124 K, while the ratio C/sub 5/2//C/sub 3/2/ = 1.0 indicates that the present magnetic interaction is of long range order character. On the other hand, fluctuations of the exchange interaction constant are found to decrease with increasing temperature. Some information regarding the directions of the magnetic moments are obtained during the study of the magnetic anisotropy course. The values of the Einstein and Debye temperatures as measured from the thermal shift results are theta/sub E/ = 250 K and theta/sub D/ = 350 K,And from the Moessbauer factor measurements theta/sub E/ = 165 K and theta/sub D/ = 285 K. (autho=r)

  16. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  17. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  18. Perforating metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Takenobu Ohashi

    2015-01-01

    Full Text Available We describe a case of metastatic malignant melanoma on the thigh with comedo-like appearance, which histologically showed elimination of tumor cells. A 70 year-old man was diagnosed with a nodular type malignant melanoma involving the lower back with satellite lesions (stage IIIB, T4b N2c M0, Breslow’s tumor thickness; 10.3 mm, Clark’s level; IV.

  19. Disseminated malignant melanoma

    Directory of Open Access Journals (Sweden)

    Verma Kaushal

    1999-01-01

    Full Text Available A 25-year-old man had multiple asymptomatic, nodular lesions on the trunk, extremities and the face for 3 months. He also had left facial palsy with severe headache and vomiting. There were no other systemic or constitutional symptoms. Skin biopsy from a nodular lesion showed features of malignant melanoma, confirmed by Fontana Masson and S-100 protein staining. A diagnosis of disseminated malignant melanoma was made and the patient was treated symptomatically. The patient died in 4 months.

  20. Radioimmunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Kovacs, J.; Chatterton, B.E.; Muecke, J.; Penglis, S.

    1999-01-01

    Full text: Malignant choroidal melanoma is one of the most common primary intraocular neoplasms. Despite significant advances in indirect ophthalmology, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and fluoroescein angiography, choroidal melanomas may be difficult to distinguish from other malignant and non-malignant eye lesions. Radioimmunoscintigraphy (RIS) with 99 Tc m -labelled monoclonal antibody F(ab')2 fragments was performed on three patients (2 females, 1 male) who were suspected of having a choroidal melanoma. Patients were injected with 240-420 MBq Technemab-K-1 and scanned 6 and 22 h post-injection. Both planar and single photon emission tomographic (SPET) imaging were performed. RIS was faintly positive in one patient in whom the diagnosis of choroidal melanoma was confirmed by enucleation of the left eye. In the other two patients, immunoscintigraphy was negative. One patient had a benign choroidal haemangioma and the other an amelanotic melanoma. This was confirmed on clinical follow-up. These preliminary results indicate that this procedure may have utility for choroidal melanoma

  1. An epigenetic vaccine model active in the prevention and treatment of melanoma

    OpenAIRE

    Magner William J; Khan A Nazmul H; Tomasi Thomas B

    2007-01-01

    Abstract Background Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. Methods HDACi-treated B16 melanoma ce...

  2. Proliferation kinetics of a human malignant melanoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    The technique of labelled mitoses and flow cytometric DNA analysis were used to determine the proliferation kinetics of a human malignant melanoma grown in nude mice. The effect of tumour volume and of long-term serial transplantation on the kinetic parameters was investigated. The results showed...... of the G1 duration time, whereas no significant changes occurred in the duration of the S and G2 phases of the cell cycle. The stability of the investigated tumour characteristics indicated that the kinetics of this melanoma remained unchanged during more than sixty serial transplantations in nude mice...

  3. Curcumin analog DM-1 in monotherapy or combinatory treatment with dacarbazine as a strategy to inhibit in vivo melanoma progression.

    Science.gov (United States)

    Faião-Flores, Fernanda; Quincoces Suarez, José Agustín; Fruet, Andréa Costa; Maria-Engler, Silvya Stuchi; Pardi, Paulo Celso; Maria, Durvanei Augusto

    2015-01-01

    Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects.

  4. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr

    2016-10-01

    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.Main variables: The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  5. An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3β/β-Catenin Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Li Yin

    2017-11-01

    Full Text Available Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-ylmethoxyphenyl-3-phenylprop-2-en-1-one (PMPP was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP in this study. Further investigations revealed that Akt and GSK3β were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.

  6. Penurunan Aktivitas Tirosinase dan Jumlah Melanin oleh Fraksi Etil Asetat Buah Malaka (Phyllantus emblica) pada Mouse Melanoma B16 Cell-Line

    OpenAIRE

    Reti Hindritiani; Diah Dhianawaty; Muchtan Sujatno; Endang Sutedja; Setiawan

    2013-01-01

    Melanin accumulation can lead to hyperpigmentation, and if it occurs on the face can cause psychosocial problem. Depigmenting agents derived from plants are increasingly utilized. Agents being developed have to be effective in inhibiting melanin synthesis and should not be toxic to melanocyte. This study aimed was to examine the effect of ethyl acetate fraction from Phyllanthus emblica (P. emblica) fruit, also known as malaka fruit, towards melanine synthesis, which was measured from the mela...

  7. Antitumor activity of N-acetyl-D-glucosamine-substituted glycoconjugates and combined therapy with keyhole limpet hemocyanin in B16F10 mouse melanoma model

    Czech Academy of Sciences Publication Activity Database

    Huliková, Katarína; Grobárová, Valeria; Křivohlavá, Romana; Fišerová, Anna

    2010-01-01

    Roč. 55, č. 5 (2010), s. 528-532 ISSN 0015-5632 R&D Projects: GA AV ČR IAA500200620; GA AV ČR IAA601680801; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : IN-VIVO * CYTOTOXICITY * LIGANDS Subject RIV: EC - Immunology Impact factor: 0.977, year: 2010

  8. Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells.

    Science.gov (United States)

    Yu, Ji Sun; Kim, An Keun

    2010-08-24

    Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis.

  9. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  10. Intracerebral metastases from ocular melanoma.

    OpenAIRE

    Jones, D. R.; Scobie, I. N.; Sarkies, N. J.

    1988-01-01

    A blind painful eye may harbour an unsuspected malignant melanoma. We report a case of ocular melanoma that presented with confusion owing to direct extension via the optic nerve into the anterior cranial fossa.

  11. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

    DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

    Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

  12. Advanced Melanoma Facebook Live Event

    Science.gov (United States)

    In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

  13. Melanoma exosomes promote mixed M1 and M2 macrophage polarization.

    Science.gov (United States)

    Bardi, Gina T; Smith, Mary Ann; Hood, Joshua L

    2018-05-01

    Macrophages are key participants in melanoma growth and survival. In general, macrophages can be classified as M1 or M2 activation phenotypes. Increasing evidence demonstrates that melanoma exosomes also facilitate tumor survival and metastasis. However, the role of melanoma exosomes in directly influencing macrophage function is poorly understood. Herein, we investigated the hypothesis that natural melanoma exosomes might directly influence macrophage polarization. To explore this hypothesis, ELISA, RT-qPCR, and macrophage functional studies were performed in vitro using an established source of melanoma exosomes (B16-F10). ELISA results for melanoma exosome induction of common M1 and M2 cytokines in RAW 264.7 macrophages, revealed that melanoma exosomes do not polarize macrophages exclusively in the M1 or M2 direction. Melanoma exosomes induced the M1 and M2 representative cytokines TNF-α and IL-10 respectively. Further assessment, using an RT-qPCR array with RAW 264.7 and primary macrophages, confirmed and extended the ELISA findings. Upregulation of markers common to both M1 and M2 polarization phenotypes included CCL22, IL-12B, IL-1β, IL-6, i-NOS, and TNF-α. The M2 cytokine TGF-β was upregulated in primary but not RAW 264.7 macrophages. Pro-tumor functions have been attributed to each of these markers. Macrophage functional assays demonstrated a trend toward increased i-NOS (M1) to arginase (M2) activity. Collectively, the results provide the first evidence that melanoma exosomes can induce a mixed M1 and M2 pro-tumor macrophage activation phenotype. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Hmgb1-IL-23-IL-17-IL-6-Stat3 Axis Promotes Tumor Growth in Murine Models of Melanoma

    Directory of Open Access Journals (Sweden)

    Qiu Tang

    2013-01-01

    Full Text Available In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, IL-17 deficiency results in reduced melanoma tumor size, diminished numbers of proliferating cells and blood vessels, and decreased percentage of CD11b+Gr-1+ MDSCs in tumor tissues. IL-17 promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066 in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth. Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17−/− mice results in markedly increased tumor size and p-Stat3 expression, whereas additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits melanoma tumor growth and reduces production of IL-23 and IL-17. All these data suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor development in murine models of melanoma, and blocking any portion of this axis will attenuate melanoma tumor growth.

  15. ORAL AMELANOTIC MELANOMA FEATURE ARTICLE

    African Journals Online (AJOL)

    hard palate (more than 40%) and the gingiva2. Melanomas arise from the uninhibited proliferation ... Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of .... head and neck region reported that amelanotic melanomas had a 20% survival at 3 years, ...

  16. Genetic Abnormalities in Uveal Melanoma

    NARCIS (Netherlands)

    N.C. Naus (Nicole)

    2001-01-01

    textabstractMelanocytic tumours are believed to arise from the neural crest-derived melanocytes. Five to twelve percent of all melanomas are located in the eye, making it, after the skin, the second most common site of melanomas (Egan et al., 1988; Chang et al., 1998). Uveal melanoma is the most

  17. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu

    2011-01-01

    Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies we...

  18. Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: A potential treatment for melanoma.

    Science.gov (United States)

    Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; Longo, João Paulo Figueiró; Silva, Jaqueline Rodrigues; Fascineli, Maria Luiza; de Souza, Paulo; Faria, Fernando; Degterev, Igor Anatolievich; Rodriguez, Anselmo; Carneiro, Fabiana Pirani; Lucci, Carolina Madeira; Escobar, Patricia; Amorim, Rivadávio Fernandes Batista; Azevedo, Ricardo Bentes

    2017-01-01

    Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy. Copyright © 2016. Published by Elsevier B.V.

  19. Enhanced expression of melanoma progression markers in mouse model of sleep apnea

    Directory of Open Access Journals (Sweden)

    S. Perini

    2016-07-01

    Full Text Available Introduction: Obstructive sleep apnea has been associated with higher cancer incidence and mortality. Increased melanoma aggressivity was reported in obstructive sleep apnea patients. Mice exposed to intermittent hypoxia (IH mimicking sleep apnea show enhanced melanoma growth. Markers of melanoma progression have not been investigated in this model. Objective: The present study examined whether IH affects markers of melanoma tumor progression. Methods: Mice were exposed to isocapnic IH to a nadir of 8% oxygen fraction for 14 days. One million B16F10 melanoma cells were injected subcutaneously. Immunohistochemistry staining for Ki-67, PCNA, S100-beta, HMB-45, Melan-A, TGF-beta, Caspase-1, and HIF-1alpha were quantified using Photoshop. Results: Percentage of positive area stained was higher in IH than sham IH group for Caspase-1, Ki-67, PCNA, and Melan-A. The greater expression of several markers of tumor aggressiveness, including markers of ribosomal RNA transcription (Ki-67 and of DNA synthesis (PCNA, in mice exposed to isocapnic IH than in controls provide molecular evidence for a apnea–cancer relationship. Conclusions: These findings have potential repercussions in the understanding of differences in clinical course of tumors in obstructive sleep apnea patients. Further investigation is necessary to confirm mechanisms of these descriptive results. Keywords: Apnea, Melanoma, Biological markers

  20. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203 Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11 )CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212 Pb labeled DOTA-Re(Arg 11 )CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212 Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  1. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  2. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    -DOTA-Re(Arg11)CCMSH and {sup 212}Pb-DOTA-Re(Arg11)CCMSH complexes were developed and synthesized to investigate its ability to target and deliver an effective dose to small melanoma tumors and metastatic deposits. Dosimetry calculations for {sup 188}Re-CCMSH and {sup 212}Pb/{sup 212}Bi[DOTA]-Re(Arg11)CCMSH were compared in the B16/F1 mouse melanoma flank tumor model to analyze the delivered dose to tumor and normal organs.

  3. Phenolic melanin precursors provide a rational approach to the design of antitumor agents for melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Jimbow, K.; Miura, T.; Ito, S.; Ishikawa, K.

    1989-01-01

    A unique biological property of the melanocyte, melanin synthesis may permit a rational approach to design agents for better management of malignant melanoma. This in vivo and in vitro study examined the selective melanocytotoxicity and antimelanoma effects of phenolic compounds, cysteinylphenol (CP), cysteaminylphenol (CAP), and related compounds, and found (1) that both 4-S-CP and 4-S-CAP are melanin precursors, (2) that 4-S-CAP possesses a marked depigmenting potency with selective destruction of melanocytes in black follicles, and (3) a significant inhibition in the protein synthesis and tumor growth of B16 melanoma. Importantly, a whole body autoradiography indicated that these phenolic melanin precursors are selectively incorporated into melanoma tissues after i.p. administration.

  4. Chemoprevention of Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2013-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens have been used extensively for protecting from UV-induced skin cancer, results of correlative population based studies are controversial, requiring further authentication to conclusively confirm the chemoprotective efficacy of sunscreens. Certain studies suggest increased skin-cancer rates in sunscreen users. Therefore, effective chemopreventive agents for preventing melanoma are urgently required. This book-chapter, reviews the current understanding regarding melanoma chemoprevention and the various strategies used to accomplish this objective. PMID:22959032

  5. The Immunology of Melanoma.

    Science.gov (United States)

    Ko, Jennifer S

    2017-09-01

    The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma. Markers to predict response to immunotherapy are currently imperfect, and the subject of intense research, which will guide the future of ancillary pathologic testing in this setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Gene transfer-applied BNCT (g-BNCT) for amelanotic melanoma in brain. Further upregulation of {sup 10}B uptake by cell modulation

    Energy Technology Data Exchange (ETDEWEB)

    Iwakura, M.; Tamaki, N. [Kobe Univ. (Japan). School of Medicine; Kondoh, H.; Mishima, Y. [Mishima Inst. for Dermatol. Res., Kobe, Hyogo (Japan); Hiratsuka, J. [Kawasaki Medical School, Dept. Radiation Oncol., Kurashiki, Okayama (Japan)

    2000-10-01

    Our success in eradicating melanoma by single BNCT with BPA led to the next urgent theme, i.e. application of such BNCT for currently uncurable melanoma metastasis in brain. In order to establish {sup 10}B-BPA-BNCT for melanoma in brain, we have investigated the pharmacokinetics of BPA which is most critical factor for successful BNCT, in melanotic and amelanotic and further tyrosinase gene-transfected amelanotic melanoma proliferating in brain having blood-brain-barrier, as compared to melanoma proliferating in skin. We have established three implanted models for melanoma in brain: 1) A1059 cells, amelanotic melanoma, 2) B16B15b cells, melanotic melanoma cells, highly metastatic to brain, and 3) TA1059 cells, with active melanogenesis induced by tyrosinase gene transfection. We would like to report the results of comparative analysis of the BPA uptake ability in these melanoma cells in both brain and skin. Based on these findings, we are further investigating to enhance {sup 10}B-BPA uptake by not only g-BNCT but also by additional melanogenesis upregulating cell modulation. (author)

  7. Gene transfer-applied BNCT (g-BNCT) for amelanotic melanoma in brain. Further upregulation of 10B uptake by cell modulation

    International Nuclear Information System (INIS)

    Iwakura, M.; Tamaki, N.; Hiratsuka, J.

    2000-01-01

    Our success in eradicating melanoma by single BNCT with BPA led to the next urgent theme, i.e. application of such BNCT for currently uncurable melanoma metastasis in brain. In order to establish 10 B-BPA-BNCT for melanoma in brain, we have investigated the pharmacokinetics of BPA which is most critical factor for successful BNCT, in melanotic and amelanotic and further tyrosinase gene-transfected amelanotic melanoma proliferating in brain having blood-brain-barrier, as compared to melanoma proliferating in skin. We have established three implanted models for melanoma in brain: 1) A1059 cells, amelanotic melanoma, 2) B16B15b cells, melanotic melanoma cells, highly metastatic to brain, and 3) TA1059 cells, with active melanogenesis induced by tyrosinase gene transfection. We would like to report the results of comparative analysis of the BPA uptake ability in these melanoma cells in both brain and skin. Based on these findings, we are further investigating to enhance 10 B-BPA uptake by not only g-BNCT but also by additional melanogenesis upregulating cell modulation. (author)

  8. Irradiated riboflavin diminishes the aggressiveness of melanoma in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Daisy Machado

    Full Text Available Melanoma is one of the most aggressive skin cancers due to its high capacity to metastasize. Treatment of metastatic melanomas is challenging for clinicians, as most therapeutic agents have failed to demonstrate improved survival. Thus, new candidates with antimetastatic activity are much needed. Riboavin (RF is a component of the vitamin B complex and a potent photosensitizer. Previously, our group showed that the RF photoproducts (iRF have potential as an antitumoral agent. Hence, we investigated the capacity of iRF on modulating melanoma B16F10 cells aggressiveness in vitro and in vivo. iRF decreases B16F10 cells survival by inhibiting mTOR as well as Src kinase. Moreover, melanoma cell migration was disrupted after treatment with iRF, mainly by inhibition of metalloproteinase (MMP activity and expression, and by increasing TIMP expression. Interestingly, we observed that the Hedgehog (HH pathway was inhibited by iRF. Two mediators of HH signaling, GLI1 and PTCH, were downregulated, while SUFU expression (an inhibitor of this cascade was enhanced. Furthermore, inhibition of HH pathway signaling by cyclopamine and Gant 61 potentiated the antiproliferative action of RF. Accordingly, when a HH ligand was applied, the effect of iRF was almost completely abrogated. Our findings indicate that Hedgehog pathway is involved on the modulation of melanoma cell aggressiveness by iRF. Moreover, iRF treatment decreased pulmonary tumor formation in a murine experimental metastasis model. Research to clarify the molecular action of flavins, in vivo, is currently in progress. Taken together, the present data provides evidence that riboflavin photoproducts may provide potential candidates for improving the efficiency of melanoma treatment.

  9. Angiogenesis and Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ribatti, Domenico, E-mail: ribatti@anatomia.uniba.it; Annese, Tiziana; Longo, Vito [Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico 70124, Bari (Italy)

    2010-02-25

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described.

  10. Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

    Science.gov (United States)

    Franco-Molina, Moisés A; Miranda-Hernández, Diana F; Mendoza-Gamboa, Edgar; Zapata-Benavides, Pablo; Coronado-Cerda, Erika E; Sierra-Rivera, Crystel A; Saavedra-Alonso, Santiago; Taméz-Guerra, Reyes S; Rodríguez-Padilla, Cristina

    2016-01-01

    Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25+ expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25+ than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4+ cells (CD4+, CD4+CD25+, and CD4+CD25+Foxp3+) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment. PMID:26834483

  11. Tumor stem cells (CD271, c-kit, SOX10) in Melanomas: prognostic and outcome implications.

    Science.gov (United States)

    Mohamed, Amr; Gonzalez, Raul S; Lawson, Diane; Wang, Jason; Cohen, Cynthia

    2014-01-01

    Melanoma cells that express stem cell marker CD271 are shown to form tumors when transplanted into nude or immunodeficient mice. These tumors have a higher metastatic potential and worse prognosis than melanomas resulting from transplantation of CD271-negative cells. We studied stem cell markers (CD271, c-kit, SOX1O) in melanomas, correlating their presence with prognostic factors and outcome. A total of 82 melanomas in tissue microarrays were immunostained for CD271, c-kit, and SOX10. Results were correlated with clinicopathologic prognostic parameters (Breslow depth of invasion, Clark level, sentinel lymph node status, and pathologic stage) and outcome (recurrence, metastases, and death). Of the 82 melanomas, CD271 was expressed in 18 (21%), c-kit in 47 (57%), and SOX10 in all (100%). CD271 does show correlation with metastases (P=0.05). c-kit is associated with favorable prognostic parameters [Breslow depth (Pmelanomas studied. In conclusion, CD271 expression in melanomas is associated with increased frequency of metastases, and c-kit immunoreactivity is associated with favorable prognostic parameters and improved outcome.

  12. Donor-Derived Conjunctival-Limbal Melanoma After a Keratolimbal Allograft.

    Science.gov (United States)

    Sepsakos, Lorena; Cheung, Albert Y; Nerad, Jeffrey A; Mogilishetty, Gautham; Holland, Edward J

    2017-11-01

    To report a single case of donor-derived conjunctival-limbal melanoma that occurred after a keratolimbal allograft (KLAL). Case report and literature review. A 56-year-old white woman with a history of bilateral limbal stem cell deficiency developed a donor-related melanoma after a KLAL. Three months after undergoing an uncomplicated KLAL, the patient presented with hemorrhagic nodules within her conjunctiva and transplanted tissue. Excisional biopsy was performed, and the pathology results revealed melanoma cells. Although the donor of the KLAL had a history of metastatic melanoma, the ocular tissue was in compliance with all eye bank requirements for donation. After discovery of the tumor, the patient's systemic immunosuppression was stopped. Within 1 week, the patient demonstrated a dramatic improvement in the size of the lesion. One month after the initial biopsy, the KLAL tissue was excised, and a pathology report revealed that there were no viable tumor cells on the ocular surface. As the limbal stem cell deficiency recurred, the eye underwent placement of a Boston type 1 keratoprosthesis. We present a case of conjunctival-limbal melanoma after a KLAL from a donor who had a history of metastatic melanoma. In response to this case, the US eye banking guidelines were amended to include stricter parameters for vascularized ocular tissue transplantation.

  13. Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets: A CONNECTION TO HEMATOGENOUS METASTASIS*

    OpenAIRE

    Lonsdorf, Anke S.; Krämer, Björn F.; Fahrleitner, Manuela; Schönberger, Tanja; Gnerlich, Stephan; Ring, Sabine; Gehring, Sarah; Schneider, Stefan W.; Kruhlak, Michael J.; Meuth, Sven G.; Nieswandt, Bernhard; Gawaz, Meinrad; Enk, Alexander H.; Langer, Harald F.

    2011-01-01

    A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothel...

  14. Hair transplant

    Science.gov (United States)

    ... this procedure: Scarring Unnatural-looking tufts of new hair growth It is possible that the transplanted hair will ... Most hair transplants result in excellent hair growth within several ... may be needed to create best results. The replaced hairs are ...

  15. Transplant rejection

    Science.gov (United States)

    ... Shortness of breath and less ability to exercise (heart transplant) Yellow skin color and easy bleeding (liver transplant) ... accountability. A.D.A.M. is among the first to achieve this important distinction for online health ...

  16. Intestine Transplant

    Science.gov (United States)

    ... to know FAQ Living donation What is living donation? Organs Types Being a living donor First steps Being ... Nursing Care of the Renal Transplant Recipient." UNOS Donation and Transplantation Nursing Curriculum . 1996 This Web site is intended ...

  17. Islet Transplantation

    Science.gov (United States)

    ... be successful. However, transplanting islet cells has several advantages over transplanting a pancreas. First, unlike the pancreas ... Email: Sign Up Thank you for signing up ' + ' '); $('.survey-form').show(); }, success: function (data) { $('#survey-errors').remove(); $('. ...

  18. Boron nanoparticles inhibit turnour growth by boron neutron capture therapy in the murine B16-OVA model

    DEFF Research Database (Denmark)

    Petersen, Mikkel Steen; Petersen, Charlotte Christie; Agger, Ralf

    2008-01-01

    Background: Boron neutron capture therapy usually relies on soluble, rather than particulate, boron compounds. This study evaluated the use of a novel boron nanoparticle for boron neutron capture therapy. Materials and Methods: Two hundred and fifty thousand B16-OVA tumour cells, pre......-incubated with boron nanoparticles for 12 hours, were injected subcutaneously into C57BL16J mice. The tumour sites were exposed to different doses of neutron radiation one, four, or eight days after tumour cell inoculation. Results: When the tumour site was irradiated with thermal neutrons one day after injection......, tumour growth was delayed and the treated mice survived longer than untreated controls (median survival time 20 days (N=8) compared with 10 days (N=7) for untreated mice). Conclusion: Boron nanoparticles significantly delay the growth of an aggressive B16-OVA tumour in vivo by boron neutron capture...

  19. Metastatic melanoma imaging with an {sup 111}In-labeled lactam bridge-cyclized {alpha}-melanocyte-stimulating hormone peptide

    Energy Technology Data Exchange (ETDEWEB)

    Guo Haixun; Shenoy, Nalini; Gershman, Benjamin M.; Yang, Jianquan [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Sklar, Larry A. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Pathology, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)], E-mail: ymiao@salud.unm.edu

    2009-04-15

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized {sup 111}In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {l_brace}DOTA-GlyGlu-CycMSH{r_brace} could be an effective imaging probe for metastatic melanoma detection. Methods: {sup 111}In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of {sup 111}In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of {sup 111}In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using {sup 111}In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) positron emission tomography (PET) imaging. Results: {sup 111}In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. {sup 111}In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. {sup 111}In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00{+-}0.74%ID/g at 2 h post-injection and 1.83{+-}0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08{+-}0.08%ID/g and 0.05{+-}0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with {sup 111}In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [{sup 18}F]FDG 1 h post-injection. Conclusions: {sup 111}In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging

  20. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

    Directory of Open Access Journals (Sweden)

    Trindade Edvaldo S

    2009-08-01

    Full Text Available Abstract Background Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM, used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180. Methods Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells. Results Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+ lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes. Conclusion Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells.

  1. Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

    Directory of Open Access Journals (Sweden)

    Tomasz Wasiewicz

    2015-03-01

    Full Text Available Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH2D3 limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH2D3 and 25(OHD3, and novel relatively non-calcemic ones (20(OHD3, calcipotriol, 21(OHpD, pD and 20(OHpL, on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OHpL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.

  2. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Congenital uveal melanoma?

    Science.gov (United States)

    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V

    2016-01-01

    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...

  5. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  6. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  7. Communication about melanoma and risk reduction after melanoma diagnosis.

    Science.gov (United States)

    Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

    2017-12-01

    Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Inhibitory effect of quercetin isolated from rose hip (Rosa canina L.) against melanogenesis by mouse melanoma cells.

    Science.gov (United States)

    Fujii, Takashi; Saito, Morio

    2009-09-01

    We investigated the effects of compounds isolated from a methanolic extract of rose hips on melanin biosynthesis in B16 mouse melanoma cells and the possible mechanisms responsible for the inhibition of melanin biosynthesis. We found that, among the isolated compounds, quercetin was a particularly potent melanogenesis inhibitor. To reveal the mechanism for this inhibition, the effects on tyrosinase of B16 mouse melanoma were measured. Quercetin decreased the intracellular tyrosinase activity as well as the tyrosinase activity in a cell culture-free system. We also examined the cellular level of tyrosinase protein and found that quercetin dose-dependently inhibited tyrosinase protein expression. We consider from these results that the inhibition of melanogenesis by quercetin was due to the inhibition of both tyrosinase activity and of the protein expression.

  9. Human melanoma metastasis in NSG mice correlates with clinical outcome in patients.

    Science.gov (United States)

    Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R; Johnson, Timothy M; Morrison, Sean J

    2012-11-07

    Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in nonobese diabetic/severe combined immunodeficient interleukin-2 receptor-γ chain null (NSG) mice. We show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, whereas stage IIIB/C melanomas that did not form distant metastases within 22 to 50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the presence of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. The study of NSG mice can therefore yield information about the metastasis of human melanomas in vivo, in this case revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and to metastasize.

  10. Human malignant melanoma heterotransplanted to nude mice.

    Science.gov (United States)

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

  11. Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Tzu-Yen [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Chang, Chia-Che [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, 91 Hsueh Shih Road, Taichung 40402, Taiwan (China); Lin, Chun-Ting [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Lai, Cong-Hao [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Department of Life Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Peng, Shao-Yu; Ko, Yi-Ju [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Tang, Pin-Chi, E-mail: pctang@dragon.nchu.edu.tw [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China)

    2011-02-15

    Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

  12. Melanoma Epidemiology and Public Health

    Science.gov (United States)

    Berwick, Marianne; Erdei, Esther; Hay, Jennifer

    2013-01-01

    Melanoma has presented a conundrum to physicians and prevention researchers. We should be able to reduce incidence and mortality rather easily because evolving melanoma lesions are observable on the surface of the skin. However, melanoma has not proved tractable. The incidence and mortality have risen in all developed countries during the past 50 years. However, mortality appears to be abating among younger cohorts even though the reason for this is not clear. PMID:19254665

  13. Melanoma and immunotherapy bridge 2015

    OpenAIRE

    Nanda, Vashisht G. Y.; Peng, Weiyi; Hwu, Patrick; Davies, Michael A.; Ciliberto, Gennaro; Fattore, Luigi; Malpicci, Debora; Aurisicchio, Luigi; Ascierto, Paolo Antonio; Croce, Carlo M.; Mancini, Rita; Spranger, Stefani; Gajewski, Thomas F.; Wang, Yangyang; Ferrone, Soldano

    2016-01-01

    Table of contents MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancin...

  14. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Ramya Chockalingam

    2015-06-01

    Full Text Available Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed.

  15. Nodular amelanotic melanoma

    Directory of Open Access Journals (Sweden)

    Nalamwar Rashmi

    2010-01-01

    Full Text Available We report a case of 65-year-old male patient who presented with multiple erythematous papules coalescing to form a nodular mass over posterior aspect of right thigh of six months duration. His general and systemic examinations were within normal range except for right inguinal lymphadenopathy. Biopsy from the lesion was done, which showed diffuse infiltrate of nests of atypical melanocytes extending upto reticular dermis. Malignant cells were positive for S100 and human melanin black 45(HMB 45. Hence, a diagnosis of amelanotic melanoma (AM - Clarke level IV and TNM stage III was reached. MRI of involved leg showed fungating soft tissue mass in the posterolateral aspect of right thigh and metastatic right inguinal adenopathy. Fine needle aspiration cytology (FNAC from the right inguinal nodes confirmed metastasis of melanoma. The patient was referred to oncosurgery department for further management.

  16. Evaluation of cytotoxic effect of methanolic extracts isolated from endemic plants of Chaharmahal va Bakhtiari province on PC-3, MCF-7, Hep G2, CHO and B16-F10 cell lines

    Directory of Open Access Journals (Sweden)

    Z. Tayarani-Najaran

    2017-11-01

    Full Text Available Background and objectives: To date, thousands of secondary metabolites have been isolated from plants and microorganisms and there is an unprecedented attention towards potential biomedical applications of natural compounds. In this study, cytotoxic properties of methanol extracts of Stachys obtusicrena, Aristolochia olivieri, Linum album, Dionysia sawyeri, Ajuga chamaecistus, Achillea kellalensis, Nepeta glomerulosa, Phlomis aucheria, Tanacetum dumosum, Dianthus orientalis, Scutellaria multicaulis, Cicer oxyodon and Picris oligocephalum which are widely grown in Iran, were investigated on PC-3 (prostat cancer, MCF-7 (breast cancer, Hep-G2 (liver cancer, CHO (ovarian cancer and B16-F10 (melanoma cell lines. Methods: The cancer cells were cultured in RPMI-1640 and incubated with different concentrations of the plant extracts. Cell viability was quantitated by Alamar blue® assay. The apoptotic cells were determined by PI coloring and Flow Cytometry (Sub-G1 peak. Results: The methanol extracts of D. sawyeri, S. obtusicrena, and C. oxyodon significantly decreased the viability of CHO cells. The Methanol extract of D. sawyer and L. album had cytotoxic effects on B16-F10 cells, whereas no toxicity was observed in MCF-7, Hep-G2 and PC-3 cell lines after incubation of the cancer cells with the plant extracts. The PI staining results showed that D. sawyeri, S. obtusicrena, and C. oxyodon in CHO cancer cells could induce apoptosis in a concentration-dependent manner. Conclusion: Screening plants to find the most cytotoxic extract showed D. sawyeri, S. obtusicrena, C. oxyodon and L. album had the potential for further analysis toward finding active phytochemicals with cytotoxic activity.

  17. Dermoscopy of difficult-to-diagnose Melanomas

    Directory of Open Access Journals (Sweden)

    Papageorgiou Chrysoula

    2016-09-01

    Full Text Available Dermoscopy is a non-invasive procedure that allows the evaluation of cutaneous lesions, and is considered to be a useful tool that improves the diagnostic accuracy of melanoma. Many dermoscopic criteria of melanoma have been established and several algorithms have been created for melanoma detection. However, the recognition of some melanomas remains challenging. Melanomas on specific body sites, melanomas in patients with multiple atypical moles, and nodular melanomas represent the most difficult-to-recognize melanoma subtypes, since they typically lack the “classic” melanoma-specific criteria. This paper provides an update on dermoscopy of difficult-to-diagnose melanomas by summarizing the newest data. Lastly, we highlight the importance of digital dermoscopy in the follow-up of melanocytic lesions for the detection of incipient melanomas while maintaining a low excision rate.

  18. Topical treatment of all-trans retinoic acid inhibits murine melanoma partly by promoting CD8+T-cell immunity.

    Science.gov (United States)

    Yin, Wei; Song, Yan; Liu, Qing; Wu, Yunyun; He, Rui

    2017-10-01

    All-trans retinoic acid (atRA), the main biologically active metabolite of vitamin A, has been implicated in immunoregulation and anti-cancer. A recent finding that vitamin A could decrease the risk of melanoma in humans indicates the beneficial role of atRA in melanoma. However, it remains unknown whether topical application of atRA could inhibit melanoma growth by influencing tumour immunity. We demonstrate topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD8 + T-cell responses, as evidenced by significantly increased proportions of effector CD8 + T cells expressing granzyme B, tumour necrosis factor-α, or interferon-γ, and Ki67 + proliferating CD8 + T cells in atRA-treated tumours compared with vaseline controls. Furthermore, topical atRA treatment promoted the differentiation of effector CD8 + T cells in draining lymph nodes (DLN) of tumour-bearing mice. Interestingly, atRA did not affect tumoral CD4 + T-cell response, and even inhibited the differentiation of interferon-γ-expressing T helper type 1 cells in DLN. Importantly, we demonstrated that the tumour-inhibitory effect of atRA was partly dependent on CD8 + T cells, as CD8 + T-cell depletion restored tumour volumes in atRA-treated mice, which, however, was still significantly smaller than those in vaseline-treated mice. Finally, we demonstrated that atRA up-regulated MHCI expression in B16F10 cells, and DLN cells from tumour-bearing mice had a significantly higher killing rate when culturing with atRA-treated B16F10 cells. Hence, our study demonstrates that topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8 + T cells. © 2017 John Wiley & Sons Ltd.

  19. Circulating melanoma cells and survival in metastatic melanoma

    NARCIS (Netherlands)

    Rao, C.; Bui, T.; Connelly, M.; Doyle, G.; Karydis, I.; Middleton, M. R.; Clack, G.; Malone, M.; Coumans, F. A. W.; Terstappen, L. W. M. M.

    2011-01-01

    A validated assay for the enumeration of circulating melanoma cells (CMCs) may facilitate the development of more effective therapies for metastatic melanoma patients. In this study CD146(+) cells were immunomagnetically enriched from 7.5 ml of blood. Isolated cells were fluorescently stained with

  20. Topical and Targeted Delivery of siRNAs to Melanoma Cells Using a Fusion Peptide Carrier.

    Science.gov (United States)

    Ruan, Renquan; Chen, Ming; Sun, Sijie; Wei, Pengfei; Zou, Lili; Liu, Jing; Gao, Dayong; Wen, Longping; Ding, Weiping

    2016-07-04

    Topical application of siRNAs through the skin is a potentially effective strategy for the treatment of melanoma tumors. In this study, we designed a new and safe fusion peptide carrier SPACE-EGF to improve the skin and cell penetration function of the siRNAs and their targeting ability to B16 cells, such that the apoptosis of B16 cells can be induced. The results show that the carrier is stable and less toxic. The EGF motif does not affect the skin and cell penetration function of the SPACE. Because EGF can strongly bind EGFR, which is overexpressed in cancer cells, the targeting ability of the SPACE-EGF-siRNA complex is increased. In vitro experiments indicate that GAPDH siRNAs conjugated with SPACE-EGF can significantly reduce the GAPDH concentration in B16 cells, and c-Myc siRNAs can cause the gene silencing of c-Myc and thus the apoptosis of cells. In vivo experiments show that the topical application of c-Myc siRNAs delivered by SPACE-EGF through the skin can significantly inhibit the growth of melanoma tumors. This work may provide insight into the development of new transdermal drug carriers to treat a variety of skin disorders.

  1. Carinal transplantation.

    OpenAIRE

    Ueda, H; Shirakusa, T

    1992-01-01

    BACKGROUND: Current techniques of management of carinal lesions are not always satisfactory. Carinal transplantation, if feasible, would be valuable in certain circumstances. METHODS AND RESULTS: Carinal transplantation experiments were performed in dogs. In early cross transplant experiments there were problems in controlling ventilation and in obtaining satisfactory anastomoses, and the animals failed to live for even a few days. In seven subsequent experiments the carinal graft was removed...

  2. Liver Transplant

    Science.gov (United States)

    ... Nutrition Clinical Trials Primary Biliary Cholangitis Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Liver Transplant View or Print All Sections Definition & ...

  3. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  4. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  5. Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on melanoma subcutaneous xenografts and lung metastases

    International Nuclear Information System (INIS)

    Kedinger, Valerie; Erbacher, Patrick; Bolcato-Bellemin, Anne-Laure; Meulle, Aline; Zounib, Omar; Bonnet, Marie-Elise; Gossart, Jean-Baptiste; Benoit, Elodie; Messmer, Melanie; Shankaranarayanan, Pattabhiraman; Behr, Jean-Paul

    2013-01-01

    Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics. We used our newly developed sticky siRNA-based technology delivered with linear polyethyleneimine (PEI) to inhibit the expression of survivin and cyclin B1 both in vitro and in vivo, and addressed the effect of this inhibition on B16-F10 murine melanoma tumor development. We confirm that survivin and cyclin B1 downregulation through a RNA interference mechanism induces a blockage of the cell cycle as well as impaired proliferation of B16-F10 cells in vitro. Most importantly, PEI-mediated systemic delivery of sticky siRNAs against survivin and cyclin B1 efficiently blocks growth of established subcutaneaous B16-F10 tumors as well as formation and dissemination of melanoma lung metastases. In addition, we highlight that inhibition of survivin expression increases the effect of doxorubicin on lung B16-F10 metastasis growth inhibition. PEI-mediated delivery of sticky siRNAs targeting genes involved in tumor progression such as survivin and cyclin B1, either alone or in combination with chemotherapeutic drugs, represents a promising strategy for melanoma treatment

  6. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  7. Histopathological findings concerning ocular melanomas.

    Science.gov (United States)

    Costache, Mariana; Pătraşcu, Oana Maria; Dumitru, Adrian; Costache, Diana; Voinea, Liliana Mary; Simionescu, Olga; Sajin, Maria

    2014-01-01

    Ocular melanoma is rare in clinical practice. In this study, we present three cases of ocular melanoma surgically removed in the Department of Ophthalmology of the Emergency University Hospital of Bucharest, Romania, and diagnosed in the Department of Pathology of the same hospital using conventional histopathological techniques and immunohistochemical tests.

  8. Angiogenic profile of uveal melanoma.

    NARCIS (Netherlands)

    Notting, I.C.; Missotten, G.S.; Sijmons, B.; Boonman, Z.F.; Keunen, J.E.E.; Pluijm, G. van der

    2006-01-01

    Uveal melanoma develops in one of the most capillary-rich tissues of the body and is disseminated hematogenously. Knowledge of the nature and the spatiotemporal expression of angiogenic factors in uveal melanoma is essential to the development of new treatment strategies, especially with regard to

  9. Archaeosome Adjuvant Overcomes Tolerance to Tumor-Associated Melanoma Antigens Inducing Protective CD8+ T Cell Responses

    Directory of Open Access Journals (Sweden)

    Lakshmi Krishnan

    2010-01-01

    Full Text Available Vesicles comprised of the ether glycerolipids of the archaeon Methanobrevibacter smithii (archaeosomes are potent adjuvants for evoking CD8+ T cell responses. We therefore explored the ability of archaeosomes to overcome immunologic tolerance to self-antigens. Priming and boosting of mice with archaeosome-antigen evoked comparable CD8+ T cell response and tumor protection to an alternate boosting strategy utilizing live bacterial vectors for antigen delivery. Vaccination with melanoma antigenic peptides TRP181-189 and Gp10025-33 delivered in archaeosomes resulted in IFN-γ producing antigen-specific CD8+ T cells with strong cytolytic capability and protection against subcutaneous B16 melanoma. Targeting responses against multiple antigens afforded prolonged median survival against melanoma challenge. Entrapment of multiple peptides within the same vesicle or admixed formulations were both effective at evoking CD8+ T cells against each antigen. Melanoma-antigen archaeosome formulations also afforded therapeutic protection against established B16 tumors when combined with depletion of T-regulatory cells. Overall, we demonstrate that archaeosome adjuvants constitute an effective choice for formulating cancer vaccines.

  10. Study of dermatoses in kidney transplant patients*

    Science.gov (United States)

    de Lima, Alexandre Moretti; da Rocha, Sheila Pereira; Reis Filho, Eugênio Galdino de Mendonça; Eid, Danglades Resende Macedo; Reis, Carmelia Matos Santiago

    2013-01-01

    BACKGROUND The increasing in the number of kidney transplant recipients has favored, more frequently than before, the emergence of dermatoses and warranted their study through subsequent publications. OBJECTIVES to evaluate the frequency of dermatoses in kidney transplant recipients. METHODS kidney transplant recipients with suspected dermatoses between March 1st 2009 and June 30th 2010. RESULTS 53 patients (28 males and 25 females), aged between 22 and 69 (mean age = 45 years) were evaluated. Most of them came from the cities of Ceilândia, Samambaia and São Sebastião/DF, and had already been transplanted for 5 to 10 years before (37.7%); 62.3% were recipients of living donors and 83% were prednisone-treated. The most prevalent dermatoses were of fungal (45.3%) and viral (39.6%) etiologies. Among the non-melanoma malignant neoplasms, the basal cell carcinoma prevailed (six cases), in spite of the low incidence. Concerning fungal dermatoses, 12 cases of onychomycosis, five of pityriasis versicolor and four of pityrosporum folliculitis were reported. For diagnosis, in most cases (64.2%), laboratory examinations (mycological and histopathological) were performed. CONCLUSION cutaneous manifestations in kidney transplant recipients are generally secondary to immunosuppression. The infectious dermatoses, especially those of fungal origin, are frequently found in kidney transplant recipients and their occurrence increases progressively according to the time elapsed from the transplantation, which makes follow-up important. PMID:23793196

  11. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  12. Comparative Aspects of Canine Melanoma

    Directory of Open Access Journals (Sweden)

    Adriana Tomoko Nishiya

    2016-02-01

    Full Text Available Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.

  13. ????????????? ??????????? ????????? ?? ???????? ???? ? ??????? ??????????????? ???????? ?????? ???????? ???? ????? B16F10

    OpenAIRE

    ????, ?????; ???????, ??????; ????????, ??????; ????????, ????????; ????????, ????

    2011-01-01

    ? ?????????? ??????????? ???????? ???? ?? ??? ???? ?????????? ???????? 3-???????????(?????????)?????? ?? ????? ???????????? ??????????????????. ?????? ????????? ??????????? ??????? ????????? ??? ???????? ???????? ???????? ?? ????????????? ??????.

  14. Corneal Transplantation

    DEFF Research Database (Denmark)

    Hjortdal, Jesper Østergaard

    Corneal transplantation has been performed for more than 100 years. Until 15 years ago the state-of-the art type of transplantation was penetrating keratoplasty, but since the start of this millennium, newly designed surgical techniques have developed considerably. Today, the vast majority of ker...

  15. Heart transplant

    Science.gov (United States)

    ... hospital for 7 to 21 days after a heart transplant. The first 24 to 48 hours will likely be in ... follow your self-care instructions. Biopsies of the heart muscle are ... after transplant, and then less often after that. This helps ...

  16. Lung transplant

    Science.gov (United States)

    ... transplant surgery include: You are placed on the heart-lung machine. One or both of your lungs are removed. For people who are having a double lung transplant, most or all of the steps from the first side are completed before the second side is ...

  17. em cultura de células de melanoma

    Directory of Open Access Journals (Sweden)

    Fernanda Vieira Berti

    2007-01-01

    Full Text Available Identification, extraction, isolation and characterization of plant derived active molecules that modulate cell viability are of great clinical and pharmacological interest. Phytochemical tests have been used to demonstrate the presence of several compounds both from the primary and secondary metabolism of Aloe vera L. Aloin, an anthraquinone isolated from the chlorophyll parenchyma of A. vera L, is known for its biological activity. The antitumoral activity of aloin and the chlorophyll parenchyma extract was evaluated in vitro with the use of murine melanoma cell line B16F10. Cells incubated with 5% CO 2 at 37ºC were treated with different aloin and parenchyma extract concentrations. Both affected cellular stability, acting as modulators of tumoral cell viability. Experimental data were fitted to a developed mathematical model. From the fitting parameters we concluded that the chlorophyll parenchyma extract is 2.3 times more toxic to the cell than aloin.

  18. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    Science.gov (United States)

    2017-11-15

    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  19. Carinal transplantation.

    Science.gov (United States)

    Ueda, H; Shirakusa, T

    1992-01-01

    BACKGROUND: Current techniques of management of carinal lesions are not always satisfactory. Carinal transplantation, if feasible, would be valuable in certain circumstances. METHODS AND RESULTS: Carinal transplantation experiments were performed in dogs. In early cross transplant experiments there were problems in controlling ventilation and in obtaining satisfactory anastomoses, and the animals failed to live for even a few days. In seven subsequent experiments the carinal graft was removed from one dog and transplanted into a second dog. Two dogs lived for over four months with immunosuppression. CONCLUSION: The results suggest that carinal transplantation can succeed if (1) the calibre of the graft is matched with that of the recipient; (2) there is an abundant blood supply to the graft; (3) appropriate immunosuppression is provided; (4) ventilation is adequate during surgery. Images PMID:1465758

  20. Histological Types of Polypoid Cutaneous Melanoma II

    OpenAIRE

    Knežević, Fabijan; Duančić, Vjekoslav; Šitić, Sanda; Horvat-Knežević, Anica; Benković, Vesna; Ramić, Snježana; Kostović, Krešimir; Ramljak, Vesna; Velemir Vrdoljak, Danko; Stanec, Mladen; Božović, Angelina

    2007-01-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex a...

  1. Brachytherapy of choroidal melanomas

    International Nuclear Information System (INIS)

    Brady, L.W.; Hernandez, J.C.

    1992-01-01

    In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including irridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques. (orig./MG) [de

  2. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  3. Dermoscopy of melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Babino, G; Lallas, A; Longo, C; Moscarella, E; Alfano, R; Argenziano, G

    2015-10-01

    Skin cancer is a major health problem because of its high incidence in white populations, as well as its related potential morbidity and mortality. Dermoscopy is a noninvasive tool that allows the identification of specific morphological features in different skin tumors, improving significantly the early diagnosis of melanoma and non-melanoma skin cancer (NMSC). This tool has also gained increased interest in the management of NMSC therapy and in the post-treatment follow-up. In this article, we provide a review of the dermoscopic patterns and criteria for the diagnosis of melanoma and NMSC described until now in the literature.

  4. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

    Science.gov (United States)

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

    2017-01-01

    The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

  5. Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ju; Isern, Nancy G.; Burton, Sarah D.; Hu, Jian Z.

    2013-10-31

    NMR metabolomics, consisting of solid state high resolution (hr) magic angle spinning (MAS) 1H NMR (1H hr-MAS), liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver . The melanoma group can be differentiated from its control group by PCA analysis of the absolute concentrations or by the absolute peak intensities of metabolites from either 1H hr-MAS NMR data on intact liver tissues or liquid state 1H-NMR spectra on liver tissue extracts. In particular, we found that the absolute concentrations of alanine, glutamate, creatine, creatinine, fumarate and cholesterol are elevated in the melanoma group as compared to controls, while the absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acylglycerol are decreased. The ratio of glycerophosphocholine to phosphocholine is increased by about 1.5 fold in the melanoma group, while the absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.

  6. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Queiroz, Rodrigo Guimaraes

    2012-01-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  7. Localized CD47 blockade enhances immunotherapy for murine melanoma.

    Science.gov (United States)

    Ingram, Jessica R; Blomberg, Olga S; Sockolosky, Jonathan T; Ali, Lestat; Schmidt, Florian I; Pishesha, Novalia; Espinosa, Camilo; Dougan, Stephanie K; Garcia, K Christopher; Ploegh, Hidde L; Dougan, Michael

    2017-09-19

    CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies. We generated a nanobody, A4, that blocks the CD47-SIRPα interaction. A4 synergizes with anti-PD-L1, but not anti-CTLA4, therapy in the syngeneic B16F10 melanoma model. Neither increased dosing nor half-life extension by fusion of A4 to IgG2a Fc (A4Fc) overcame the issue of an antigen sink or, in the case of A4Fc, systemic toxicity. Generation of a B16F10 cell line that secretes the A4 nanobody showed that an enhanced response to several immune therapies requires near-complete blockade of CD47 in the tumor microenvironment. Thus, strategies to localize CD47 blockade to tumors may be particularly valuable for immune therapy.

  8. Inhibition of CSF-1R supports T-cell mediated melanoma therapy.

    Directory of Open Access Journals (Sweden)

    Marjolein Sluijter

    Full Text Available Tumor associated macrophages (TAM can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+ myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors.

  9. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  10. Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cristina Santoriello

    2010-12-01

    Full Text Available Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed.Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period.This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

  11. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  12. GM3 ganglioside: a novel target for the therapy against melanoma

    International Nuclear Information System (INIS)

    Mazorra, Zaima; Mesa, Cirse; Fernandez, Luis E

    2009-01-01

    Malignant melanoma is a tumor with a steeply increasing incidence and scarce therapeutic options once metastatic. Currently, no vaccine is widely commercially available for melanoma treatment or prevention. The overexpression of GM3 ganglioside in murine and human melanomas and its important role in tumor progression makes this self antigen a potential target for preventive immunotherapy of this neoplasm. Previously, we have shown that preventive vaccination with GM3/VSSP induced a specific antitumor response; and elicited the rejection of syngeneic GM3-positive melanoma cells in immunized mice. In the present paper, we published the induction of a potent antitumor effect of this vaccine administered in a minimal residual disease B16 melanoma model. These findings propose the GM3/VSSP vaccine as a therapy designed to elicit and/or boost antitumor immunity in patients with minimal residual disease after surgery; thereby preventing or prolonging the time to recurrence. This is an important issue of the clinical setting because patients with stage II melanoma were reported to have 60% chance of survival 5 years after surgery. In addition, we examined the mechanisms by which this immunogen confers tumor protection. Surprisingly, in spite of the glycolipidic nature of this antigen, we have found that induction of anti-GM3 IgG antibodies and tumor- specific IFN γ secreting CD8+ T cells correlated with tumor protection. As a result, these findings demonstrate, for the first time, the direct involvement of the cellular immune response in the anti-tumor protection induced by a ganglioside-based vaccine

  13. Blocking Tumor Necrosis Factor α Enhances CD8 T-cell-Dependent Immunity in Experimental Melanoma.

    Science.gov (United States)

    Bertrand, Florie; Rochotte, Julia; Colacios, Céline; Montfort, Anne; Tilkin-Mariamé, Anne-Françoise; Touriol, Christian; Rochaix, Philippe; Lajoie-Mazenc, Isabelle; Andrieu-Abadie, Nathalie; Levade, Thierry; Benoist, Hervé; Ségui, Bruno

    2015-07-01

    TNF plays a dual, still enigmatic role in melanoma, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. Herein, the tumor growth of melanoma cell lines expressing major histocompatibility complex class I molecules at high levels (MHC-I(high)) was dramatically impaired in TNF-deficient mice, and this was associated with enhanced tumor-infiltrating CD8(+) T lymphocytes. Immunodepletion of CD8 T cells fully restored melanoma growth in TNF(-/-) mice. Systemic administration of Etanercept inhibited MHC-I(high) melanoma growth in immunocompetent but not in immunodeficient (IFNγ(-/-), nude, or CD8(-/-)) mice. MHC-I(high) melanoma growth was also reduced in mice lacking TNF-R1, but not TNF-R2. TNF(-/-) and TNF-R1(-/-) mice as well as Etanercept-treated WT mice displayed enhanced intratumor content of high endothelial venules surrounded by high CD8(+) T-cell density. Adoptive transfer of activated TNF-R1-deficient or -proficient CD8(+) T cells in CD8-deficient mice bearing B16K1 tumors demonstrated that TNF-R1 deficiency facilitates the accumulation of live CD8(+) T cells into the tumors. Moreover, in vitro experiments indicated that TNF triggered activated CD8(+) T cell death in a TNF-R1-dependent manner, likely limiting the accumulation of tumor-infiltrating CD8(+) T cells in TNF/TNF-R1-proficient animals. Collectively, our observations indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8(+) T-cell accumulation and may serve as a putative target to favor CD8(+) T-cell-dependent immune response in melanoma. ©2015 American Association for Cancer Research.

  14. Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

    Directory of Open Access Journals (Sweden)

    Franco-Molina MA

    2016-01-01

    Full Text Available Moisés A Franco-Molina,* Diana F Miranda-Hernández,* Edgar Mendoza-Gamboa, Pablo Zapata-Benavides, Erika E Coronado-Cerda, Crystel A Sierra-Rivera, Santiago Saavedra-Alonso, Reyes S Taméz-Guerra, Cristina Rodríguez-Padilla Immunology and Virology Department, Biological Sciences Faculty, University Autonoma of Nuevo León (UANL, San Nicolás de los Garza, Nuevo León, Mexico*These authors contributed equally to this work Abstract: Forkhead box p3 (Foxp3 expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold], protein (flow cytometry [0.02%], CD25+ expression (0.06%, cellular proliferation (trypan blue staining, and interleukin (IL-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL] than those in B16F10 wild-type (WT cells (P<0.05. Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment expressed relatively lower levels of Foxp3 and CD25+ than B16F10 WT cells (P<0.05 in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4+ cells (CD4+, CD4+CD25+, and CD4+CD25+Foxp3+ increased in a time-dependent manner (P<0.05 in tumors derived from B16F10 WT cells

  15. Superficial melanomas of oral mucous membranes.

    Science.gov (United States)

    Regezi, J A; Hayward, J R; Pickens, T N

    1978-05-01

    In accordance with microscopic and clinical criteria established for superficial melanomas of the skin (superficial spreading melanoma, lentigo maligna melanoma, acral-lentiginous melanoma), three oral lesions have been evaluated. The literature on oral melanomas has also been reviewed, with special attention given to those cases that had pre-existing melanosis. One patient with a diagnosis of superficial spreading melanoma eventually died of his untreated lesion 11 years after its first appearance. Two patients had lesions diagnosed as acral-lentiginous melanoma (a group which also includes volar and subungual melanomas) that exhibited aggressive, recurrent behavior. These lesions had microsocpic features similar to lentigo maligna melanoma but did not behave in a manner consistent with that diagnosis. Electron microscopic study of one acral-lentiginous melanoma demonstrated malenosomes and premelanosomes that were like those seen in normal melanocytes and nevus cells. The superficial or radial growth phase of many oral melanomas has apparently gone unrecognized. Melanosis has been reported to be a common feature of invasive oral melanomas but has not generally been related to the natural history of these lesions. Oral lesions with a prolonged intra-epithelial or radial growth phase would be expected to have a better prognosis than nodular melanomas, but meaningful survival data are not available because of the infrequency with which oral melanomas have been subclassified.

  16. Primary dermal melanoma: a West Australian cohort.

    Science.gov (United States)

    Teow, James; Chin, Olivia; Hanikeri, Mark; Wood, Benjamin A

    2015-09-01

    The objectives of this study were to identify a subgroup of patients with putative primary dermal melanoma after thorough multidisciplinary clinical and histological evaluation, and to describe the clinical, histological and selected molecular features of these lesions. The records of the Western Australian Melanoma Advisory Service were searched for potential cases of primary dermal melanoma. The clinical and histological features were reviewed, immunohistochemical assessment was performed and clinical outcomes recorded. Eighteen cases of putative primary dermal melanoma with available clinical data were identified. Two of 12 cases in which further histological sections could be obtained were excluded because of the presence of findings suggesting an epidermal origin on these further sections. In one additional case, such origin could not be histologically excluded. Median follow-up period for the remaining cases was 68 months. Confirmed primary dermal melanoma accounts for 0.87% of cases of melanoma referred to a subspecialist melanoma advisory service. These cases show significant histological overlap with dermal/subcutaneous metastases of melanoma, but display a relatively good prognosis, with a 5-year survival of 87.5%. Our results support the recognition of a distinct group of melanoma that mimics metastatic melanoma, but is associated with a relatively favourable outcome. The group of putative primary dermal melanoma is likely to be heterogenous, including cases of primary nodular melanoma in which epidermal connection has not been identified, metastatic melanoma with an occult primary lesion and true primary dermal melanoma. © 2015 Royal Australasian College of Surgeons.

  17. Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database

    DEFF Research Database (Denmark)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri

    2018-01-01

    BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. METHODS: We...... estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics...... in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI, 94-99) and 100...

  18. High accuracy of family history of melanoma in Danish melanoma cases

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...... probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree...

  19. Organ Transplantation

    Science.gov (United States)

    ... here for a deeper conversation on this topic led by Hastings Director of Research Josephine Johnston. Sorry, ... accept people without insurance. Transplant teams rarely consider anyone over 75 years of age. Some centers exclude ...

  20. Hair Transplants

    Science.gov (United States)

    ... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Hair Transplants Before (left) and after (right) - top ...

  1. Cornea Transplant

    Science.gov (United States)

    ... Swelling of the cornea Signs and symptoms of cornea rejection In some cases, your body's immune system ... the risks of the procedure. Finding a donor cornea Most corneas used in cornea transplants come from ...

  2. Liver Transplant

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Liver Transplant Back In ...

  3. Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy.

    Science.gov (United States)

    Viallard, Claire; Chezal, Jean-Michel; Mishellany, Florence; Ranchon-Cole, Isabelle; Pereira, Bruno; Herbette, Aurélie; Besse, Sophie; Boudhraa, Zied; Jacquemot, Nathalie; Cayre, Anne; Miot-Noirault, Elisabeth; Sun, Jian-Sheng; Dutreix, Marie; Degoul, Françoise

    2016-03-15

    Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresistance and increase targeted radionuclide therapy (TRT) efficacy. In human SK-Mel 3 melanoma xenograft, the addition of coDbait had a synergistic effect on tumor growth and median survival. The anti-tumor effect was additive in murine syngeneic B16Bl6 model whereas coDbait combination with [131I]ICF01012 did not increase TRT side effects in secondary pigmented tissues (e.g. hair follicles, eyes). Our results confirm that DNA lesions induced by TRT were not enhanced with coDbait association but, the presence of micronuclei and cell cycle blockade in tumor shows that coDbait acts by interrupting or delaying DNA repair. In this study, we demonstrate for the first time, the usefulness of DNA repair traps in the context of targeted radionuclide therapy.

  4. Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice.

    Science.gov (United States)

    Nishikawa, Tomoyuki; Tung, Li Yu; Kaneda, Yasufumi

    2014-12-01

    Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses.

  5. Suppression of tumorigenicity and metastatic potential of melanoma cells by transduction of interferon gene

    Directory of Open Access Journals (Sweden)

    Lykhova A. A.

    2014-01-01

    Full Text Available The aim of this study was to investigate an inhibitory effect of baculovirus-mediated transduction of the murine interferon-beta gene on mouse melanoma in vitro and in vivo. Methods. Studies were performed on B16 mouse melanoma (MM-4 cell line. Transduction, immunocytochemical and tumor cell biology approaches have been used in this study. Results. Transduction of MM-4 cells by the recombinant baculovirus with IFN-beta gene is accompanied by morphological changes of tumor cells, suppression of cell proliferation, significant inhibition of platting efficiency of cells and their colonies formation in semisolid agar. Moreover, transduction of melanoma MM-4 cells by the baculovirus IFN-transgene leads to inhibition of tumorigenicity and metastatic ability of the cells in vivo. The intravenous administration of recombinant baculovirus vector with IFN gene inhibits growth of metastases induced in the lungs of mice by intravenously injected tumor cells. Conclusions. Transduction of mouse melanoma cells by the recombinant baculovirus with murine IFN-beta gene inhibits their proliferative potential, tumorigenicity and metastatic activity.

  6. Inhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Longfei Huo

    Full Text Available BACKGROUND: hTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress growth of xenografted glioblastoma in nude mice. Although ectopic expression of hTERTC27 upregulated genes that are involved in apoptosis, cell cycle, and immune response, the mechanism for hTERTC27-induced tumor suppression has not been completely elucidated. Since hTERT was identified as a universal tumor-associated antigen, we hypothesize that hTERTC27 inhibits tumor growth in vivo through activation of anti-tumor immune response. METHODOLOGY/PRINCIPAL FINDING: Immunocompetent C57BL/6 mice were used for mouse B16 melanoma model. Mice bearing B16 melanoma were administered rAAV-/rAdv viral cocktail expressing hTERTC27, and tumor growth was monitored after viral cocktail treatment. Blood and splenocytes were used to determine the level of cytokines and the activity of immune cells, respectively. B16 tumor growth was significantly inhibited by subcutaneous administration of a single dose of 1.5×10(11 vg rAAV-hTERTC27 and 2.5×10(9 pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27. The population and cytotoxicity of NK cells in the mice were significantly augmented by rAAV-/rAdv-hTERTC27 treatment, and selective depletion of the NK cell population in mice by intraperitoneal injection of anti-GM1 antibody abrogated the growth suppression of melanoma induced by rAAV-/rAdv-hTERTC27 administration. CONCLUSION: Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.

  7. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  8. Blood flow velocity imaging of malignant melanoma by micro multipoint laser Doppler velocimetry

    Science.gov (United States)

    Ishida, H.; Andoh, T.; Akiguchi, S.; Shirakawa, H.; Kobayashi, D.; Kuraishi, Y.; Hachiga, T.

    2010-09-01

    We have developed a laser Doppler velocimeter to measure blood flow, the micromultipoint laser Doppler velocimeter (μ-MLDV). This equipment can measure absolute velocity and, based on this, can display the course of blood vessels. In this study, we attempted to perform blood flow velocity imaging of malignant melanoma transplanted to the mouse ear. We found that blood flow velocity of the formed blood vessels originating in the melanoma was much greater than that of the capillary vessels in normal skin. Furthermore, the form of the tumor was clearly visible from the blood flow velocity image. These experimental results suggest that μ-MLDV has potential as a diagnostic method for distinguishing benign nevi from malignant melanomas.

  9. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  10. Case studies of skin melanoma

    Directory of Open Access Journals (Sweden)

    A. V. Kozlova

    2015-01-01

    Full Text Available Skin melanoma is a malignant tumor originating in the cells of the melanocytic system, which is characterized by an aggressive clinical course, significant metastatic potential and unfavorable prognosis. These features of the tumor stipulate the need to improve measures to optimize early diagnosis of tumors. The article presents cases of pigmented skin melanoma to demonstrate the variability of clinical manifestations of this tumor requiring dermatologist skills in the differential diagnostics of neoplasms.

  11. [Choroidal melanoma - evolution and prognosis].

    Science.gov (United States)

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  12. Umbilicus reconstruction after melanoma excision

    Directory of Open Access Journals (Sweden)

    Miguel Costa-Silva

    2017-01-01

    Full Text Available An 81-year-old woman was admitted with a nodular cutaneous melanoma of the abdominal wall involving the umbilicus. After performing wide excision with 2 cm margin of the melanoma, umbilical reconstruction and defect closure were planned. After careful consideration, we decided to use an island pedicle flap which allowed closure of the defect and reconstruction of the umbilicus.

  13. The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm) on melanoma in vitro and in vivo

    International Nuclear Information System (INIS)

    Frigo, Lúcio; Luppi, Juliana SS; Favero, Giovani M; Maria, Durnavei A; Penna, Sócrates C; Bjordal, Jan M; Bensadoun, Rene J; Lopes-Martins, Rodrigo AB

    2009-01-01

    It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10) in vitro and the in vivo development of melanoma in mice after laser irradiation. We performed a controlled in vitro study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The in vivo mouse model (male Balb C, n = 21) of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days) with a 660 nm 50 mW CW laser, beam spot size 2 mm 2 , irradiance 2.5 W/cm 2 and irradiation times of 60s (dose 150 J/cm 2 ) and 420s (dose 1050 J/cm 2 ) respectively. There were no statistically significant differences between the in vitro groups, except for an increase in the hypodiploid melanoma cells (8.48 ± 1.40% and 4.26 ± 0.60%) at 72 h post-irradiation. This cancer-protective effect was not reproduced in the in vivo experiment where outcome measures for the 150 J/cm 2 dose group were not significantly different from controls. For the 1050 J/cm 2 dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups. LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm 2 ) and high dose (1050 J/cm 2 ) significantly increases melanoma tumor growth in vivo

  14. Kidney-Pancreas Transplant

    Science.gov (United States)

    ... Menu Menu Search Home Prevention Kidney Disease Patients Organ Donation & Transplantation Professionals Events Advocacy Donate A to Z Health ... Tests for Transplant Care After Kidney Transplant Common Organ Donation and Transplantation Terms The National Kidney Foundation (NKF) is the ...

  15. Experimental stress analysis and fatigue tests of five 24-in. NPS ANSI Standard B16. 9 tees. [PWR; BWR

    Energy Technology Data Exchange (ETDEWEB)

    Moore, S.E.; Hayes, J.K.; Weed, R.A.

    1985-03-01

    Experimental stress analyses and low-cycle fatigue tests of five 24-in. nominal pipe size American National Standards Institute (ANSI) Standard B16.9 forged tees are documented in this report. The tees, designated as Oak Ridge National Laboratory tees T10, T11, T12, T13, and T16, were tested under subcontract at Combustion Engineering, Inc. in Chattanooga, Tennessee. Experimental stress analyses were conducted for 12 individual loadings on each tee. Each test model was instrumented with approx. 225, 1/8-in. three-gage, 45/sup 0/ strain rosettes on the inside and outside surfaces; and 6 linear variable differential transformers mounted on special nonflexible holding frames for measuring deflections and rotations of the pipe extensions. Following completion of the strain-gate tests, each tee was fatigue tested to failure with either a fully reversed displacement controlled in-plane bending moment on the branch or a cyclic internal pressure that ranged from a value slightly above zero to about 90% of the nominal yield pressure of the pipe extensions.

  16. Tumor-targeting properties of {sup 90}Y- and {sup 177}Lu-labeled {alpha}-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    Energy Technology Data Exchange (ETDEWEB)

    Miao Yubin [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States) and Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States)]. E-mail: miaoy@missouri.edu; Hoffman, Timothy J. [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Quinn, Thomas P. [Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2005-07-01

    The purpose of this study was to compare the tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were 25.70{+-}4.64 and 14.48{+-}0.85 %ID/g at 2 h, and 14.09{+-}2.73 and 17.68{+-}3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.

  17. Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    International Nuclear Information System (INIS)

    Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

  18. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

    Science.gov (United States)

    Guenova, Emmanuella; Lichte, Verena; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

    2009-08-01

    Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.

  19. Biodistribution of modular nanotransporter carrying Auger electron emitter and targeted at melanoma cells in murine tumor model

    Science.gov (United States)

    Vorontsova, M. S.; Morozova, N. B.; Karmakova, T. A.; Rosenkranz, A. A.; Slastnikova, T. A.; Petriev, V. M.; Smoryzanova, O. A.; Tischenko, V. K.; Yakubovskaya, R. I.; Kaprin, A. D.; Sobolev, A. S.

    2017-09-01

    Recombinant modular nanotransporter containing α-melanocyte-stimulating hormone peptide sequence (MNT-MSH) as a ligand module was designed for nucleus-targeted delivery of cytotoxic agents into melanoma cells. MNT-MSH radiolabeled with Auger electron emitter (111In-NOTA-MNT-MSH) showed a high antitumor efficacy in mice bearing syngeneic melanoma after intratumoral (i.t.) injection. This study is aimed at evaluating the biodistribution of the radioconjugate in melanoma tumor model in vivo. 111In-NOTA-MNT-MSH was administered i.t. in C57Bl/6j mice bearing subcutaneously implanted B16-F1 murine melanoma cells, expressing high levels of MCR1. The tissue uptake of radioactivity was determined ex vivo by γ-counter measurements. The intravenous route of administration did not provide a desirable level of radioactivity accumulation in the tumor, possibly, due to a high uptake of the transporter in liver tissue. After i.t. administration 111In-NOTA-MNT-MSH provided a high local retention of radionuclide, ranged from 400 to 350 %ID/g within at least 48 hours post-injection. MNT containing Auger electron emitter and α-MSH peptide as vector ligand could be a promising basis for radiopharmaceutical preparations intended for melanoma treatment.

  20. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report.

    Science.gov (United States)

    Kwatra, Vineet; Karanth, Narayan V; Priyadarshana, Kelum; Charakidis, Michail

    2017-03-19

    Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection. We present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma. He was treated with first-line pembrolizumab but experienced subsequent graft failure and rapid disease progression. This case highlights the risks associated with the administration of checkpoint inhibitors in patients with a renal transplant and on immunosuppressive therapy. More specifically, it adds to the literature indicating that, compared with the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab, anti-programmed cell death protein 1 agents are more likely to lead to renal graft failure. Additionally, these novel immunotherapeutics may be ineffective in transplant patients; therefore, clinicians should be very aware of those risks and carefully consider selection of agents and full disclosure of the risks to their patients.

  1. Mitochondrial ATF2 translocation contributes to apoptosis induction and BRAF inhibitor resistance in melanoma through the interaction of Bim with VDAC1.

    Science.gov (United States)

    Gao, Zongwei; Shang, Qingjuan; Liu, Zhaoyun; Deng, Chun; Guo, Chunbao

    2015-11-03

    The mitochondrial accumulation of ATF2 is involved in tumor suppressor activities via cytochrome c release in melanoma cells. However, the signaling pathways that connect mitochondrial ATF2 accumulation and cytochrome c release are not well documented. Several melanoma cell lines, B16F10, K1735M2, A375 and A375-R1, were treated with paclitaxel and vemurafenib to test the function of mitochondrial ATF2 and its connection to Bim and voltage-dependent anion channel 1 (VDAC1). Immunoprecipitation analysis was performed to investigate the functional interaction between the involved proteins. VDAC1 oligomerization was evaluated using an EGS-based crosslinking assay. The expression and migration of ATF2 to the mitochondria accounted for paclitaxel stimuli and acquired resistance to BRAF inhibitors. Mitochondrial ATF2 facilitated Bim stabilization through the inhibition of its degradation by the proteasome, thereby promoting cytochrome c release and inducing apoptosis in B16F10 and A375 cells. Studies using B16F10 and A375 cells genetically modified for ATF2 indicated that mitochondrial ATF2 was able to dissociate Bim from the Mcl-1/Bim complex to trigger VDAC1 oligomerization. Immunoprecipitation analysis revealed that Bim interacts with VDAC1, and this interaction was remarkably enhanced during apoptosis. These results reveal that mitochondrial ATF2 is associated with the induction of apoptosis and BRAF inhibitor resistance through Bim activation, which might suggest potential novel therapies for the targeted induction of apoptosis in melanoma therapy.

  2. The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action

    Science.gov (United States)

    2012-01-01

    Background The incidence of melanoma is considerably increasing worldwide. Frequent failing of classical treatments led to development of novel therapeutic strategies aiming at managing advanced forms of this skin cancer. Additionally, the implication of the endocannabinoid system in malignancy is actively investigated. Methods We investigated the cytotoxicity of endocannabinoids and their hydrolysis inhibitors on the murine B16 melanoma cell line using a MTT test. Enzyme and receptor expression was measured by RT-PCR and enzymatic degradation of endocannabinoids using radiolabeled substrates. Cell death was assessed by Annexin-V/Propidium iodine staining. Tumors were induced in C57BL/6 mice by s.c. flank injection of B16 melanoma cells. Mice were injected i.p. for six days with vehicle or treatment, and tumor size was measured each day and weighted at the end of the treatment. Haematoxylin-Eosin staining and TUNEL assay were performed to quantify necrosis and apoptosis in the tumor and endocannabinoid levels were quantified by HPLC-MS. Tube formation assay and CD31 immunostaining were used to evaluate the antiangiogenic effects of the treatments. Results The N-arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol and N- palmitoylethanolamine (PEA) reduced viability of B16 cells. The association of PEA with the fatty acid amide hydrolase (FAAH) inhibitor URB597 considerably reduced cell viability consequently to an inhibition of PEA hydrolysis and an increase of PEA levels. The increase of cell death observed with this combination of molecules was confirmed in vivo where only co-treatment with both PEA and URB597 led to decreased melanoma progression. The antiproliferative action of the treatment was associated with an elevation of PEA levels and larger necrotic regions in the tumor. Conclusions This study suggests the interest of targeting the endocannabinoid system in the management of skin cancer and underlines the advantage of associating

  3. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. The role of nitric oxide in melanoma.

    Science.gov (United States)

    Yarlagadda, Keerthi; Hassani, John; Foote, Isaac P; Markowitz, Joseph

    2017-12-01

    Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Tool to Distinguish Moles from Melanoma

    Science.gov (United States)

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  6. Large melanoma metastases to the gastrointestinal tract.

    OpenAIRE

    Silverman, J M; Hamlin, J A

    1989-01-01

    It is well known that malignant melanoma can metastasize widely. Although these metastases in the gastrointestinal tract usually appear as small 'bull's-eye' or 'target' lesions, there are a few reports of relatively large melanoma metastases. We report five cases of large melanoma lesions metastatic to the alimentary canal. We also emphasise the consideration of a thorough gastrointestinal tract evaluation in patients with malignant melanoma especially if they are symptomatic.

  7. Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces.

    Science.gov (United States)

    Sondak, Vernon K; Messina, Jane L

    2014-10-01

    Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Isochlorogenic acid A promotes melanin synthesis in B16 cell through the β-catenin signal pathway.

    Science.gov (United States)

    Mamat, Nuramina; Dou, Jun; Lu, Xueying; Eblimit, Aiden; Haji Akber, Aisa

    2017-09-01

    Isochlorogenic acid A, also called 3,5-dicaffeoylquinic acid (3,5-diCQA), is a widespread phenolic compound in the plant. Recent studies have shown that it has antioxidant and anti-inflammatory activity. In addition, oxidative stress and inflammation induced by solar ultraviolet radiation is a very significant reason for skin depigmentation. Therefore, in this study, we evaluated the effect of 3,5-diCQA on B16 cells and explored its molecular mechanism. Results showed that 3,5-diCQA upregulated intracellular melanin production in a time- and dose-dependent manner. Tyrosinase (TYR) activity was also increased after treatment with 3,5-diCQA in a dose-dependent manner. Expressions of TYR, TYR-related protein1, TYR-related protein2, and microphthalmia-associated transcription factor were upregulated in a dose-dependent manner after 48 h of treatment with 3,5-diCQA. Results also showed that 3,5-diCQA promoted the phosphorylation of Akt at Thr308 and glycogen synthase kinase-3β at Ser 9. Moreover, 3,5-diCQA increased the content of β-catenin in cell cytoplasm and nucleus by reducing the content of phosphorylated β-catenin (p-β-catenin). All these results suggest that 3,5-diCQA may mediate the acceleration of melanin synthesis by the β-catenin signal pathway. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    International Nuclear Information System (INIS)

    Pastila, R.

    2006-04-01

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  10. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Pastila, R.

    2006-04-15

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  11. Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals

    International Nuclear Information System (INIS)

    Chen, F.D.; Hsieh, B.T.; Wang, H.E.; Ou, Y.H.; Yang, W.K.; Whang-Peng, J.; Liu, R.S.; Knapp, F.F.; Ting, G.; Yen, S.H.

    2001-01-01

    In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. Methods: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF 1 mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10 5 B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16∼18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes ( 188 Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals

  12. Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.

    Directory of Open Access Journals (Sweden)

    Keitaro Fukuda

    Full Text Available Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN, type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular matrix proteins at the wound site was reproduced in a mouse model of wound healing, with the upregulation of Postn mRNA persisting the longest. POSTN was expressed in the region surrounding melanoma cell nests in metastatic lesions of both wounded mice and the patient. POSTN attenuated the cell adhesion and promoted the migration of melanoma cells without affecting their proliferation in vitro. In the mouse model, the wound site as well as subcutaneously injected osteoblasts that secrete large amounts of POSTN invited the metastasis of remotely-transplanted melanoma cells on the sites. Osteoblasts with suppression of POSTN by shRNA showed a greatly reduced ability to promote such metastasis. Our results suggest that POSTN is a key factor in promoting melanoma cell metastasis to wound sites by providing a premetastatic niche.

  13. Cadaveric transplantation.

    Directory of Open Access Journals (Sweden)

    Gokal R

    1993-10-01

    Full Text Available Transplantation is already the optimum treatment for terminal renal failure. Donor organ shortage means that there are large number of patients on dialysis awaiting this treatment. This has in some countries led to unacceptable unscrupulous practices of live non-related graft donation. The outcome of graft and patient after transplantation has improved significantly based on a better understanding of immunopathology, immunosuppression and tissue typing. The future is promising and xenografting may well solve the organ shortage but undoubtedly will raise other issues.

  14. Pancreas transplantation

    International Nuclear Information System (INIS)

    Snider, J.F.; Hunter, D.W.; Castaneda-Zuniga, W.R.; Letourneau, J.G.

    1989-01-01

    Pancreas transplantation can be complicated by vascular thrombosis, stenosis, or anastomotic leak, complications that predispose to transplant pancreatectomy. The relative roles of noninvasive radiologic studies in such vascular complications have been correlated with angiographic or pathologic data. The results of 54 scintigraphic studies, 25 CT studies, 16 sonograms, and 23 color Doppler examinations have been correlated with those of 40 angiograms and 28 pathologic studies in a population of 185 recipients. CT (sensitivity, 100%; specificity, 75%; accuracy, 92%) and US (sensitivity, 88%; specificity, 80%; accuracy, 85%) were most helpful in noninvasive screening for vascular complications, while angiography remains nearly definite in the radiographic diagnosis of these problems

  15. Pregnancy and early-stage melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; De Hullu, JA; Kuiper, H; Nap, RE; Hoekstra, HJ

    2003-01-01

    BACKGROUND. Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the

  16. Clinicopathological and molecular aspects of cutaneous Melanoma

    NARCIS (Netherlands)

    Bogenrieder, T.

    2009-01-01

    Clinicopathological and molecular aspects of cutaneous melanoma. Melanoma arises form the transformation of neural crest-derived melanocytes, the pigment cells of the skin, which reside in the basal layer of the epidermis. Melanoma is the deadliest form of skin cancer and one of the most aggressive

  17. Genetic prognostic factors in uveal melanoma

    NARCIS (Netherlands)

    Maat, Willem

    2012-01-01

    Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent

  18. Melanoma continues to rise throughout the world

    African Journals Online (AJOL)

    Review Article: Melanoma continues to rise throughout the world. 530 ... of melanoma. The radiation in the ultraviolet B range is said to be the critical component. Generally, worldwide, the incidence of melanoma in white people4,5 correlates inversely with .... lymphocytes, mitotic rate, regression, angiolymphatic invasion ...

  19. Decreased tumor-infiltrating lymphocytes in nodular melanomas compared with matched superficial spreading melanomas.

    Science.gov (United States)

    Lin, Richard L; Wang, Thomas J; Joyce, Cara J; Mihm, Martin C; Murphy, George F; Lian, Christine G; Lin, Jennifer Y

    2016-10-01

    Melanoma causes over 9000 deaths annually in the USA. Among its subtypes, nodular melanoma leads to a disproportionate number of fatalities compared with superficial spreading melanoma, the most common subtype. Recent breakthroughs in melanoma research have indicated a strong connection between melanoma virulence and the immune system. We hypothesize that the aggression of nodular melanoma may, in part, be because of decreased recognition by the immune system, as represented by a decreased presence of tumor-infiltrating lymphocytes (TILs), compared with its superficial spreading counterpart. Indeed, TILs on a primary melanoma have been used as a marker for immune response and have prognostic value for survival and sentinel lymph node status. After matching melanoma cases by age, sex, and Breslow thickness, we found significantly fewer TILs in nodular melanomas than in superficial spreading melanomas. This association was prominent in thin (≤2 mm) melanomas and was no longer significant in thick (>2 mm) melanomas. In addition, this difference in TILs was only present in men and not in women. Our finding suggests that nodular melanomas are more frequently associated with absent TILs, providing an avenue for further investigation into differences in immunogenicity of the primary melanoma and whether they underlie the unique virulence of nodular melanoma.

  20. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  1. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

    International Nuclear Information System (INIS)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel; Cachin, Florent; Bonnet, Mathilde; Askienazy, Serge; Dolle, Frederic

    2012-01-01

    Here, we report a new and rapid radiosynthesis of 18 F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([ 18 F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [ 18 F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [ 18 F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18 F-fluorodeoxyglucose ([ 18 F]FDG). The fully automated radiosynthesis of [ 18 F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [ 18 F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [ 18 F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [ 18 F]FDG showed that both radiotracers were able to detect melanoma lesions, but [ 18 F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [ 18 F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  2. Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

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    Liu Edison

    2007-06-01

    Full Text Available Abstract Background Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. Methods GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo. Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. Results Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain

  3. Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

    Directory of Open Access Journals (Sweden)

    Papon Janine

    2004-04-01

    Full Text Available Abstract Background Analytical imaging by secondary ion mass spectrometry (SIMS provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing. Methods The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma. B16 melanoma cells were injected intravenously to C57BL6/J1/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis. Results Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc. while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue. Conclusion This study demonstrates the potential of SIMS microscopy, which allows the

  4. Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

    OpenAIRE

    Gallagher, Martin P.; Kelly, Patrick J.; Jardine, Meg; Perkovic, Vlado; Cass, Alan; Craig, Jonathan C.; Eris, Josette; Webster, Angela C.

    2010-01-01

    Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non–skin cancer (including melanoma) and skin c...

  5. Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells.

    Science.gov (United States)

    Shen, Hongxin; Shi, Sanjun; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2015-01-01

    Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44(+) cells in vitro. In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

  6. Characterization and Inducing Melanoma Cell Apoptosis Activity of Mannosylerythritol Lipids-A Produced from Pseudozyma aphidis.

    Directory of Open Access Journals (Sweden)

    Linlin Fan

    Full Text Available Mannosylerythritol lipids (MELs are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC, self-assembling into particles in the water solution. It was observed to induce cell growth-inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down-regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS.

  7. Characterization and Inducing Melanoma Cell Apoptosis Activity of Mannosylerythritol Lipids-A Produced from Pseudozyma aphidis.

    Science.gov (United States)

    Fan, Linlin; Li, Hongji; Niu, Yongwu; Chen, Qihe

    2016-01-01

    Mannosylerythritol lipids (MELs) are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC), self-assembling into particles in the water solution. It was observed to induce cell growth-inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down-regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS).

  8. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  9. Current systemic therapies for melanoma.

    Science.gov (United States)

    Palathinkal, Darren M; Sharma, Timmie R; Koon, Henry B; Bordeaux, Jeremy S

    2014-09-01

    Systemic agents are used in melanoma for adjuvant therapy and to treat metastatic disease. Currently, interferon-α is the only agent approved for adjuvant therapy. Six drugs are FDA approved for metastatic disease: dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib and trametinib were approved in 2013. This review will update the practicing dermatologist on the differences in efficacy, adverse events, and cost of systemic therapies available for the treatment of melanoma. This article is a review of the current literature on systemic therapies for advanced melanoma. Key search words included "advanced melanoma," "systemic therapy," and "adjuvant therapy" with particular focus on the past 20 years. Before 2011, dacarbazine and IL-2 were the only FDA approved therapies for metastatic melanoma, and IFN-α is the only approved agent for adjuvant therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are the first to have improved overall survival in Phase III studies in comparison with other systemic therapies. Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

  10. Other targeted drugs in melanoma.

    Science.gov (United States)

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials.

  11. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  12. In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8 treatment in a murine melanoma model

    Directory of Open Access Journals (Sweden)

    Trindade Edvaldo S

    2010-03-01

    Full Text Available Abstract Background Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8 stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro. Methods Here we describe the in vitro inhibition of invasion and the in vivo anti-metastatic potential after M8 treatment by inhalation in the B16F10 lung metastasis model. Results We found that M8 has at least two functions, acting as both an inhibitor of cancer cell adhesion and invasion and as a perlecan expression antagonist, which are strongly correlated with several metastatic, angiogenic and invasive factors in melanoma tumors. Conclusion The findings suggest that this medication is a promising non-toxic therapy candidate by improving the immune response against tumor cells or even induce direct dormancy in malignancies.

  13. A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study

    International Nuclear Information System (INIS)

    Balivada, Sivasai; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L; Rachakatla, Raja Shekar; Wang, Hongwang; Samarakoon, Thilani N; Dani, Raj Kumar; Pyle, Marla; Kroh, Franklin O; Walker, Brandon; Leaym, Xiaoxuan

    2010-01-01

    There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe 3 O 4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe 3 O 4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art

  14. High accuracy of family history of melanoma in Danish melanoma cases.

    Science.gov (United States)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-12-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

  15. Inhibitory effect of rose hip (Rosa canina L.) on melanogenesis in mouse melanoma cells and on pigmentation in brown guinea pigs.

    Science.gov (United States)

    Fujii, Takashi; Ikeda, Katsumi; Saito, Morio

    2011-01-01

    The compounds present in rose hips exerting an inhibitory action against melanogenesis in B16 mouse melanoma cells were investigated by dividing an aqueous extract of rose hips (RE) into four fractions. The 50% ethanol eluate from a DIAION HP-20 column significantly reduced the production of melanin and was mainly composed of procyanidin glycosides. We also found that this 50% ethanol eluate reduced the intracellular tyrosinase activity and also had a direct inhibitory effect on tyrosinase obtained as a protein mixture from the melanoma cell lysate. We also investigated the effect of orally administering RE on skin pigmentation in brown guinea pigs, and found that the pigmentation was inhibited together with the tyrosinase activity in the skin. These data collectively suggest that proanthocyanidins from RE inhibited melanogenesis in mouse melanoma cells and guinea pig skin, and could be useful as a skin-whitening agent when taken orally.

  16. Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

    Science.gov (United States)

    Quinn, T J; Healy, N; Sara, A; Maggi, E; Claros, C S; Kabarriti, R; Scandiuzzi, L; Liu, L; Gorecka, J; Adem, A; Basu, I; Yuan, Z; Guha, C

    2017-01-01

    The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

  17. Eyebrow transplantation.

    Science.gov (United States)

    Goldman, G D

    2001-04-01

    Reconstruction of the eyebrow has historically been accomplished with temporal scalp pedicle flap formation or free composite scalp grafts. These two techniques may be associated with substantial morbidity and a false, overly dense eyebrow appearance. Hair transplantation of the eyebrows has been described with excellent results, but is relatively underreported in the literature. To determine whether modern techniques of micrograft hair transplantation can suitably re-create an aesthetic eyebrow in a case of iatrogenic eyebrow alopecia. A 33-year-old woman with iatrogenic eyebrow alopecia underwent four sessions of eyebrow micrograft hair transplantation to re-create both eyebrows. Suitable aesthetic eyebrows were re-created in a symmetric fashion with proper hair orientation. The process was time consuming and tedious, but highly effective. Eyebrow transplantation is a suitable alternative to pedicle flap formation and composite scalp grafting. It is a straightforward procedure that can be performed in the office under local anesthesia with minimal attendant morbidity. The result may be superior to that seen with more involved eyebrow replacement procedures.

  18. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  19. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  20. Clear cells in acral melanoma.

    Science.gov (United States)

    Schmuth, M; Spötl, L; Zelger, B; Weinlich, G; Zelger, B

    2001-01-01

    Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

  1. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  2. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  3. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Melanoma: oncogenic drivers and the immune system.

    Science.gov (United States)

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio; Rosell, Rafael

    2015-10-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches.

  5. MiR-26b inhibits melanoma cell proliferation and enhances apoptosis by suppressing TRAF5-mediated MAPK activation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Meng; Long, Chaoqin; Yang, Guilan; Luo, Yang; Du, Hua, E-mail: lemonlives_dr@163.com

    2016-03-11

    Alterations in microRNA-26b (miR-26b) expression have been shown to participate in various malignant tumor developments. However, the possible function of miR-26b in human melanoma cells remains unclarified. In this study, quantitative polymerase chain reaction was used to explore the expression profiles of miR-26b in melanoma cells. The effect of miR-26b on cell viability was determined by using MTT assays and colony formation assay. The apoptosis levels were evaluated by using Annexin V/fluorescein isothiocyanate (FITC) apoptosis detection kit and the apoptosis cells were confirmed by Transmission Electron Microscopy (TEM). Luciferase reporter plasmids were constructed to confirm direct targeting. Our study found that the expression of miR-26b was downregulated in human melanoma specimens. Overexpression of miR-26b significantly increased the anti-proliferative effects and apoptosis in A375 and B16F10 melanoma cells. In addition, luciferase gene reporter assays confirmed that TRAF5 was a direct target gene of miR-26b and the anti-tumor effect of miR-26b in melanoma cells was significantly counteracted by treatment with TRAF5 overexpression. Furthermore, the molecular mechanisms underlying the tumor suppressor of miR-26b in malignant melanomas may be due to the dephosphorylation of MAPK pathway caused by the decrease in TRAF5 expression when miR-26b is up-regulated in melanoma cells. These findings indicate that miR-26b might influence TRAF5-MAPK signaling pathways to facilitate the malignant progression of melanoma cells. - Highlights: • miR-26b is downregulated in human melanomas. • miR-26b suppressed melanoma cell proliferation and enhanced cell apoptosis. • TRAF5 is a direct target of miR-26b and inversely correlates with miR-26b expression. • miR-26b modulated MAPK signaling pathway by targeting TRAF5.

  6. Choroidal melanoma in a dog.

    Science.gov (United States)

    Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo

    2005-08-01

    A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.

  7. Oral mucosal melanoma: A case report

    Directory of Open Access Journals (Sweden)

    Ramlal Gantala

    2017-01-01

    Full Text Available Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44% and sinuses (8%. In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

  8. An epigenetic vaccine model active in the prevention and treatment of melanoma

    Directory of Open Access Journals (Sweden)

    Magner William J

    2007-12-01

    Full Text Available Abstract Background Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi, which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. Methods HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity. Results HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-γ-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity. Conclusion The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.

  9. An epigenetic vaccine model active in the prevention and treatment of melanoma.

    Science.gov (United States)

    Khan, A Nazmul H; Magner, William J; Tomasi, Thomas B

    2007-12-10

    Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity. HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-gamma-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity. The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.

  10. Viwithan, a StandardizedWithania somniferaRoot Extract Induces Apoptosis in Murine Melanoma Cells.

    Science.gov (United States)

    Sudeep, H V; Gouthamchandra, K; Venkatesh, B J; Prasad, K Shyam

    2018-01-01

    Withania somnifera is an Indian medicinal herb known for the multipotential ability to cure various therapeutic ailments as described in the ayurvedic system of medicine. In the present study, we have evaluated the antiproliferative activity of a standardized W. somnifera root extract (Viwithan) against different human and murine cancer cell lines. The cytotoxicity of Viwithan was determined using thiazolyl blue tetrazolium blue assay and crystal violet staining. The apoptotic changes in B16F1 cells following treatment with Viwithan were observed by acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation assay. The binding affinity of withanolides in Viwithan with antiapoptotic proteins B-cell lymphoma 2, B-cell lymphoma-extra large, and myeloid cell leukemia 1 (MCL-1) were studied using in silico approach. The half maximal inhibitory concentration (IC50) values of Viwithan against liver hepatocellular carcinoma, Henrietta Lacks cervical carcinoma cells, human colorectal carcinoma cell line, and Ehrlich ascites carcinoma cells were 1830, 968, 2715, and 633 μg/ml, respectively. Interestingly, Viwithan was highly effective against B16F1 cells with an IC50 value of 220 μg/ml after 24 h treatment. The morphological alterations of apoptotic cell death were clearly observed in the AO/EB-stained cells after treatment with Viwithan. Viwithan induced late apoptotic changes in treated B16F1 cells as evident by the ladder formation of fragmented DNA in a time-dependent manner. The findings of molecular docking showed that withanolides present in Viwithan have a more binding affinity with the antiapoptotic proteins, particularly MCL-1. We have reported for the first time that Viwithan with 5% withanolides has a potent cytotoxic effect, particularly against B16F1 murine melanoma cells among the different cancer cell lines tested. The present study reports for the first time that Viwithan, a standardized 5% Withania somnifera root extract, has potent

  11. Novel photosensitizers trigger rapid death of malignant human cells and rodent tumor transplants via lipid photodamage and membrane permeabilization.

    Directory of Open Access Journals (Sweden)

    Mikhail M Moisenovich

    Full Text Available BACKGROUND: Apoptotic cascades may frequently be impaired in tumor cells; therefore, the approaches to circumvent these obstacles emerge as important therapeutic modalities. METHODOLOGY/PRINCIPAL FINDINGS: Our novel derivatives of chlorin e(6, that is, its amide (compound 2 and boronated amide (compound 5 evoked no dark toxicity and demonstrated a significantly higher photosensitizing efficacy than chlorin e(6 against transplanted aggressive tumors such as B16 melanoma and M-1 sarcoma. Compound 5 showed superior therapeutic potency. Illumination with red light of mammalian tumor cells loaded with 0.1 µM of 5 caused rapid (within the initial minutes necrosis as determined by propidium iodide staining. The laser confocal microscopy-assisted analysis of cell death revealed the following order of events: prior to illumination, 5 accumulated in Golgi cysternae, endoplasmic reticulum and in some (but not all lysosomes. In response to light, the reactive oxygen species burst was concomitant with the drop of mitochondrial transmembrane electric potential, the dramatic changes of mitochondrial shape and the loss of integrity of mitochondria and lysosomes. Within 3-4 min post illumination, the plasma membrane became permeable for propidium iodide. Compounds 2 and 5 were one order of magnitude more potent than chlorin e(6 in photodamage of artificial liposomes monitored in a dye release assay. The latter effect depended on the content of non-saturated lipids; in liposomes consisting of saturated lipids no photodamage was detectable. The increased therapeutic efficacy of 5 compared with 2 was attributed to a striking difference in the ability of these photosensitizers to permeate through hydrophobic membrane interior as evidenced by measurements of voltage jump-induced relaxation of transmembrane current on planar lipid bilayers. CONCLUSIONS/SIGNIFICANCE: The multimembrane photodestruction and cell necrosis induced by photoactivation of 2 and 5 are

  12. In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model

    International Nuclear Information System (INIS)

    Pasco, Sylvie; Ramont, Laurent; Venteo, Lydie; Pluot, Michel; Maquart, Francois-Xavier; Monboisse, Jean-Claude

    2004-01-01

    Our previous studies demonstrated that a synthetic peptide encompassing residues 185-203 of the noncollagenous (NC1) domain of the α3 chain of type IV collagen, named tumstatin, inhibits in vitro melanoma cell proliferation and migration. In the present study, B16F1 melanoma cells were stably transfected to overexpress the complete tumstatin domain (Tum 1-232) or its C-terminal part, encompassing residues 185-203 (Tum 183-232). Tumstatin domain overexpression inhibited B16F1 in vitro cell proliferation, anchorage-independent growth, and invasive properties. For studying the in vivo effect of overexpression, representative clones were subcutaneously injected into the left side of C57BL6 mice. In vivo tumor growth was decreased by -60% and -56%, respectively, with B16F1 cells overexpressing Tum 1-232 or Tum 183-232 compared to control cells. This inhibitory effect was associated with a decrease of in vivo cyclin D1 expression. We also demonstrated that the overexpression of Tum 1-232 or Tum 183-232 induced an in vivo down-regulation of proteolytic cascades involving matrix metalloproteinases (MMPs), especially the production or activation of MMP-2, MMP-9, MMP-13, as well as MMP-14. The plasminogen activation system was also altered in tumors with a decrease of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) and a strong increase of plasminogen activator inhibitor-1 (PAI-1). Collectively, our results demonstrate that tumstatin or its C-terminal antitumor fragment, Tum 183-232, inhibits in vivo melanoma progression by triggering an intracellular transduction pathway, which involves a cyclic AMP (cAMP)-dependent mechanism

  13. Transplant Ethics.

    Science.gov (United States)

    Altınörs, Nur; Haberal, Mehmet

    2016-11-01

    The aim of this study was to review and discuss the great variety of ethical issues related to organ donation, organ procurement, transplant activities, and new ethical problems created as a result of technologic and scientific developments. An extensive literature survey was made, and expert opinions were obtained. The gap between demand and supply of organs for transplant has yielded to organ trafficking, organ tourism, and commercialism. This problem seems to be the most important issue, and naturally there are ethical dilemmas related to it. A wide number of ideas have been expressed on the subject, and different solutions have been proposed. The struggle against organ trafficking and commercialism should include legislation, efforts to increase deceased-donor donations, and international cooperation. China's policy to procure organs from prisoners sentenced to death is unethical, and the international community should exert more pressure on the Chinese government to cease this practice. Each particular ethical dilemma should be taken separately and managed.

  14. A {sup 99m}Tc(CO){sub 3}-labeled pyrazolyl-{alpha}-melanocyte-stimulating hormone analog conjugate for melanoma targeting

    Energy Technology Data Exchange (ETDEWEB)

    Raposinho, Paula D.; Correia, Joao D.G.; Alves, Susana [Departamento de Quimica, ITN, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Botelho, Maria F.; Santos, Ana C. [Instituto de Biofisica/Biomatematica, IBILI-Faculdade de Medicina de Coimbra, 300-548 Coimbra (Portugal); Santos, Isabel [Departamento de Quimica, ITN, Estrada Nacional 10, 2686-953 Sacavem (Portugal)], E-mail: isantos@itn.pt

    2008-01-15

    Melanoma primary tumors can be, in most cases, removed surgically, whereas there is no satisfactory treatment for metastatic melanoma, being almost always lethal at this stage. Therefore, early detection of primary melanoma tumors is essential. The finding that melanocortin-1 receptor (MC1R) is overexpressed in isolated melanoma cells and melanoma tissues led to the radiolabeling of several {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) analogs for early detection and treatment of melanoma. We have coupled the {alpha}-MSH analog Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH{sub 2}, through the {epsilon}-amino group of Lys{sup 11}, to a pyrazolyl-containing chelator (pz). The resulting pz-{alpha}-MSH analog reacted with the fac-[{sup 99m}Tc(CO){sub 3}]{sup +} moiety, giving [Ac-Nle{sup 4},Asp{sup 5},D-Phe{sup 7},Lys{sup 11}(pz-{sup 99m}Tc(CO){sub 3})]{alpha}-MSH{sub 4-11} in high yield, high specific activity and high radiochemical purity. This radioconjugate, which presents remarkable stability in vitro, exhibited time- and temperature-dependent internalization (4 h at 37{sup o}C; 56.7% maximum internalization) and high cellular retention (only 38% was released from the cell after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake [4.2{+-}0.9%ID/g, at 4 h postinjection (p.i.)] was also obtained in melanoma-bearing C57BL6 mice. The in vivo affinity and specificity of the radioconjugate to MC1R were demonstrated by receptor-blocking studies with the potent NDP-MSH agonist (63.5% reduction in tumor uptake at 4 h p.i.)

  15. Drug Repurposing Approach Identifies a Synergistic Drug Combination of an Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.

    Science.gov (United States)

    Riedel, Tina; Demaria, Olivier; Zava, Olivier; Joncic, Ana; Gilliet, Michel; Dyson, Paul J

    2018-01-02

    By screening a drug library comprising FDA approved compounds, we discovered a potent interaction between the antifungal agent haloprogin and the experimental organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The combination of these two small molecules, even at low doses, elicited an improved therapeutic response on tumor growth over either agent alone or the current treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma tumor model, where classical cytotoxic chemotherapeutic agents show little efficacy. The combination with the repurposed chemodrug haloprogin provides the basis for a new powerful treatment option for cutaneous melanoma. Importantly, because synergistic induction of tumor cell death is achieved with low individual drug doses, and cellular targets for RAPTA-T are different from those of classical chemotherapeutic drugs, a therapeutic strategy based on this approach could avoid toxicities and potentially resistance mechanisms, and could even inhibit metastatic progression.

  16. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  17. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  18. Stages of Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  19. Prognostic Factors in Uveal Melanoma

    NARCIS (Netherlands)

    E. Kiliç (Emine)

    2006-01-01

    textabstractUveal melanoma is the most common intra-ocular tumour in the western world with an annual incidence of seven per million. Approximately 50% of the patients treated by enucleation dye eventually due to metastatic disease. Besides enucleation there are nowadays more conservative treatment

  20. The EMT-related transcription factor snail up-regulates FAPα in malignant melanoma cells.

    Science.gov (United States)

    Yi, Yanmei; Wang, Zhaotong; Sun, Yanqin; Chen, Junhu; Zhang, Biao; Wu, Minhua; Li, Tianyu; Hu, Li; Zeng, Jun

    2018-03-15

    FAPα is a cell surface serine protease, mainly expressed in tumor stromal fibroblasts in more than 90% of human epithelial carcinomas. Due to its almost no expression in normal tissues and its tumor-promoting effects, FAPα has been studied as a novel potential target for antitumor therapy. However, the regulation mechanism on FAPα expression is poorly understood. In this study, we found that overexpression of snail significantly increased the mRNA and protein expression levels of FAPα in malignant melanoma B16 and SK-MEL-28 cells. Overexpression of snail increased FAPα promoter activity remarkably. Snail could directly bind to FAPα promoter to regulate FAPα expression. Moreover, snail expression was positively correlated to FAPα expression in human cutaneous malignant melanoma. Furthermore, knockdown of FAPα markedly reduced snail-induced cell migration. Overall, our findings provide a novel regulation mechanism on FAPα expression and highlight the role of snail/FAPα axis as a novel target for melanoma treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice.

    Science.gov (United States)

    Li, D; Yee, J A; Thompson, L U; Yan, L

    1999-07-19

    We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.

  2. Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression

    Directory of Open Access Journals (Sweden)

    Cox James L

    2005-05-01

    Full Text Available Abstract Background Tumor metastasis is a frequent cause of treatment failure for cancer patients. A key feature of metastatic cancer cells is their invasive ability. Cysteine proteases contribute to invasive properties of many cancer cell types. To analyze the contribution of cysteine proteases to metastasis we have over-expressed in B16 melanoma cells the natural cysteine protease inhibitor, cystatin C. We measured in vitro invasion of cystatin over-expression clones with Boyden chamber type assays. Tail-vein injections of cells were used to compare lung tumor colonization. Subcutaneous tumor growth and tumor cell metastasis from primary tumors were also analyzed. Apoptosis of tumor cells was measured in lung tissues following melanoma cell injection. Results Results show the in vitro invasion of cystatin C over-expressing cells was dramatically inhibited. Lung tumor colonization was also reduced. Increased tumor cell apoptosis was found to be an important factor and may be related to the reduced tumor burden noted in this system of melanoma metastasis. Conclusion Cysteine proteases therefore, may be a target for future anti-metastatic therapies.

  3. Stem Cell Transplant

    Science.gov (United States)

    ... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

  4. Pediatric melanoma: incidence, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Saiyed FK

    2017-04-01

    Full Text Available Faiez K Saiyed,1 Emma C Hamilton,1 Mary T Austin,1,2 1Department of Pediatric Surgery, McGovern Medical School, 2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole. Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. Keywords: melanoma, pediatric, adolescent, childhood

  5. Guideline on the Management of Melanoma | Board | South African ...

    African Journals Online (AJOL)

    Validation. Melanoma management involves many medical specialties. Guidelines should therefore be developed through a multidisciplinary consensus. The Melanoma Advisory Board consists of a forum of dermatologists, oncologists, plastic surgeons and pathologists. Guideline sponsor. The meetings of the Melanoma ...

  6. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...... is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma)....

  7. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  8. Gallium-68-labeled DOTA-rhenium-cyclized {alpha}-melanocyte-stimulating hormone analog for imaging of malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Wei Lihui [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Miao Yubin; Gallazzi, Fabio; Quinn, Thomas P. [Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65212 (United States); Welch, Michael J. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110 (United States); Vavere, Amy L. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Lewis, Jason S. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: j.s.lewis@wustl.edu

    2007-11-15

    Introduction: Diagnosis of malignant melanoma is critical, since a patient's prognosis is poor. Previous studies have shown that {sup 64}Cu- and {sup 86}Y-DOTA-ReCCMSH(Arg{sup 11}) have the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of positron emission tomography (PET). This encouraged us to investigate DOTA-ReCCMSH(Arg{sup 11}) labeled with another {beta}{sup +}-emitting radionuclide, {sup 68}Ga. Methods: DOTA-ReCCMSH(Arg{sup 11}) was successfully labeled with {sup 68}Ga at pH 3.8-4 at 85{sup o}C. Acute biodistribution and small-animal PET imaging studies were performed in mice bearing B16/F1 melanoma tumor. Results: Biodistribution studies showed moderate receptor-mediated tumor uptake, fast nontarget organ clearance and high tumor to nontarget tissue ratios. Preadministration of D-lysine significantly reduced kidney uptake without affecting the uptake of the agent in the tumor. Small-animal PET images showed that the tumor could be clearly visualized at all time points examined (0.5-2 h) with the standardized uptake value analysis following a similar trend as the biodistribution data. Conclusions: The preliminary data obtained suggest that {sup 68}Ga-DOTA-ReCCMSH(Arg{sup 11}) is a promising PET imaging agent for early detection of malignant melanoma.

  9. Risk factors for second primary melanoma among Dutch patients with melanoma

    NARCIS (Netherlands)

    Schuurman, M.S.; Waal, A.C. de; Thijs, E.J.M.; Rossum, M.M. van; Kiemeney, L.A.L.M.; Aben, K.K.H.

    2017-01-01

    BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified

  10. 17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.

    Science.gov (United States)

    Joshi, Sandeep S; Jiang, Shunlin; Unni, Emmanual; Goding, Stephen R; Fan, Tao; Antony, Paul A; Hornyak, Thomas J

    2018-01-01

    Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

  11. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  12. Molecular insights into melanoma brain metastases.

    Science.gov (United States)

    Westphal, Dana; Glitza Oliva, Isabella C; Niessner, Heike

    2017-06-01

    Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    Science.gov (United States)

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  14. Transplante uterino

    OpenAIRE

    Carvalho, Margarida Teixeira Farias Meira de, 1992-

    2016-01-01

    Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016 A infertilidade de causa uterina afecta cerca de 3-5% da população geral, sendo a adopção e a gestação de substituição as únicas opções para estes casais atingirem a parentalidade, dado que é um problema ainda sem tratamento. Nas últimas décadas, foram realizados diversos estudos animais com o objectivo de demonstrar a viabilidade, segurança e eficácia do transplante uterino como ...

  15. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  16. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  17. Giant hanging melanoma of the eyelid skin

    Directory of Open Access Journals (Sweden)

    Pai Radha

    2008-01-01

    Full Text Available Cutaneous melanoma of the eyelid is a rare entity. We present a 53-year-old male who had a nevus on the left upper eyelid skin since childhood, which transformed into a huge ulcerated hanging mass in the same region. Excision of the mass was done and histopathology confirmed the diagnosis of nodular malignant melanoma. A small preauricular lymph node showed metastatic melanoma on fine needle aspiration cytology.

  18. Intra- and inter-tumor heterogeneity in a vemurafenib-resistant melanoma patient and derived xenografts.

    Science.gov (United States)

    Kemper, Kristel; Krijgsman, Oscar; Cornelissen-Steijger, Paulien; Shahrabi, Aida; Weeber, Fleur; Song, Ji-Ying; Kuilman, Thomas; Vis, Daniel J; Wessels, Lodewyk F; Voest, Emile E; Schumacher, Ton Nm; Blank, Christian U; Adams, David J; Haanen, John B; Peeper, Daniel S

    2015-09-01

    The development of targeted inhibitors, like vemurafenib, has greatly improved the clinical outcome of BRAF(V600E) metastatic melanoma. However, resistance to such compounds represents a formidable problem. Using whole-exome sequencing and functional analyses, we have investigated the nature and pleiotropy of vemurafenib resistance in a melanoma patient carrying multiple drug-resistant metastases. Resistance was caused by a plethora of mechanisms, all of which reactivated the MAPK pathway. In addition to three independent amplifications and an aberrant form of BRAF(V600E), we identified a new activating insertion in MEK1. This MEK1(T55delins) (RT) mutation could be traced back to a fraction of the pre-treatment lesion and not only provided protection against vemurafenib but also promoted local invasion of transplanted melanomas. Analysis of patient-derived xenografts (PDX) from therapy-refractory metastases revealed that multiple resistance mechanisms were present within one metastasis. This heterogeneity, both inter- and intra-tumorally, caused an incomplete capture in the PDX of the resistance mechanisms observed in the patient. In conclusion, vemurafenib resistance in a single patient can be established through distinct events, which may be preexisting. Furthermore, our results indicate that PDX may not harbor the full genetic heterogeneity seen in the patient's melanoma. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  19. IL4-induced gene 1 promotes tumor growth by shaping the immune microenvironment in melanoma.

    Science.gov (United States)

    Bod, Lloyd; Lengagne, Renée; Wrobel, Ludovic; Ramspott, Jan Philipp; Kato, Masashi; Avril, Marie-Françoise; Castellano, Flavia; Molinier-Frenkel, Valérie; Prévost-Blondel, Armelle

    2017-01-01

    Amino acid catabolizing enzymes emerged as a crucial mechanism used by tumors to dampen immune responses. The L-phenylalanine oxidase IL-4 induced gene 1 (IL4I1) is expressed by tumor-associated myeloid cells of most solid tumors, including melanoma. We previously provided the only evidence that IL4I1 accelerates tumor growth by limiting the CD8 + T cell mediated immune response, in a mouse model of melanoma cell transplantation. Here, we explored the role of IL4I1 in Ret mice, a spontaneous model of melanoma. We found that IL4I1 was expressed by CD11b + myeloid cells and that its activity correlated with disease aggressiveness. IL4I1 did not enhance tumor cell proliferation or angiogenesis, but orchestrated the remodeling of the immune compartment within the primary tumor. Indeed, the inactivation of IL4I1 limited the recruitment of polymorphonuclear myeloid-derived suppressor cells and enhanced the infiltration by Th1 and cytotoxic T cells, thus delaying tumor development and metastatic dissemination. Accordingly, human primary melanomas that were poorly infiltrated by IL4I1 + cells exhibited a higher density of CD8 + T cells. Collectively, our findings strengthen the rationale for therapeutic targeting of IL4I1 as one of the key immune regulators.

  20. Timely Healthcare Checkup Catches Melanoma Early

    Science.gov (United States)

    ... Skin Cancer" Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma Early / NIH Research to Results / Skin and Sun – ...

  1. Genomic characterisation of acral melanoma cell lines.

    Science.gov (United States)

    Furney, Simon J; Turajlic, Samra; Fenwick, Kerry; Lambros, Maryou B; MacKay, Alan; Ricken, Gerda; Mitsopoulos, Costas; Kozarewa, Iwanka; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan; Reis-Filho, Jorge S; Herlyn, Meenhard; Murata, Hiroshi; Marais, Richard

    2012-07-01

    Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell lines display a mutation rate that is comparable to that of published primary and metastatic acral melanomas and observe a mutational signature suggestive of UV-induced mutagenesis in two of the cell lines. Mutations were identified in oncogenes and tumour suppressors previously linked to melanoma including BRAF, NRAS, KIT, PTEN and TP53, in cancer genes not previously linked to melanoma and in genes linked to DNA repair such as BRCA1 and BRCA2. Our findings provide strong circumstantial evidence to suggest that acral melanoma cell lines and acral tumours share genetic features in common and that these cells are therefore valuable tools to investigate the biology of this aggressive melanoma subtype. Data are available at: http://rock.icr.ac.uk/collaborations/Furney_et_al_2012/. © 2012 John Wiley & Sons A/S.

  2. Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

    Science.gov (United States)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David

    2018-01-15

    The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI, 94-99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87%-100% in the Cancer Registry and 93%-100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95.0% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database are high, supporting their use in epidemiologic studies.

  3. UVB: suscetibilidade no melanoma maligno

    OpenAIRE

    Nasser,Nilton

    2010-01-01

    FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61) e grup...

  4. [Acute dyspnea in malignant melanoma].

    Science.gov (United States)

    Franzen, A M; Günzel, T

    2011-09-01

    Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

  5. Neutron capture therapy for melanoma

    International Nuclear Information System (INIS)

    Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

    1988-01-01

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs

  6. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.

    2016-01-01

    with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed....../non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1...

  7. Neutron capture therapy for melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

    1988-01-01

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

  8. Thigmotropism of Malignant Melanoma Cells

    OpenAIRE

    Quatresooz, Pascale; Pi?rard-Franchimont, Claudine; No?l, Fanchon; Pi?rard, G?rald E.

    2011-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape)....

  9. Dermoscopic evaluation of nodular melanoma.

    Science.gov (United States)

    Menzies, Scott W; Moloney, Fergal J; Byth, Karen; Avramidis, Michelle; Argenziano, Giuseppe; Zalaudek, Iris; Braun, Ralph P; Malvehy, Josep; Puig, Susana; Rabinovitz, Harold S; Oliviero, Margaret; Cabo, Horacio; Bono, Riccardo; Pizzichetta, Maria A; Claeson, Magdalena; Gaffney, Daniel C; Soyer, H Peter; Stanganelli, Ignazio; Scolyer, Richard A; Guitera, Pascale; Kelly, John; McCurdy, Olivia; Llambrich, Alex; Marghoob, Ashfaq A; Zaballos, Pedro; Kirchesch, Herbert M; Piccolo, Domenico; Bowling, Jonathan; Thomas, Luc; Terstappen, Karin; Tanaka, Masaru; Pellacani, Giovanni; Pagnanelli, Gianluca; Ghigliotti, Giovanni; Ortega, Blanca Carlos; Crafter, Greg; Ortiz, Ana María Perusquía; Tromme, Isabelle; Karaarslan, Isil Kilinc; Ozdemir, Fezal; Tam, Anthony; Landi, Christian; Norton, Peter; Kaçar, Nida; Rudnicka, Lidia; Slowinska, Monika; Simionescu, Olga; Di Stefani, Alessandro; Coates, Elliot; Kreusch, Juergen

    2013-06-01

    Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. To determine the dermoscopy features of NM. Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. When

  10. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  11. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  12. Do melanoma patients with melanoma of unknown primary have better survival than patients with melanoma of known primary?

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kjerkegaard, Ulrik; Sørensen, Jens Ahm

    2018-01-01

    Background: Several studies have compared the survival rate of melanoma of unknown primary (MUP) patients with patients with a known primary melanoma (MKP). Some studies found improved survival in MUP patients, whereas others found similar or poorer outcomes. The aim of this study was to evaluate...

  13. Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

    NARCIS (Netherlands)

    Paolino, G.; Bekkenk, M. W.; Didona, D.; Eibenschutz, L.; Richetta, A. G.; Cantisani, C.; Viti, G.; Carbone, A.; Buccini, P.; de Simone, P.; Ferrari, A.; Scali, E.; Calvieri, S.; Silipo, V.; Cigna, E.; Viti, G. P.; Bottoni, U.

    2016-01-01

    Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an

  14. Snake venoms components with antitumor activity in murine melanoma cells; Componentes derivados de venenos de serpentes com acao antitumoral em celulas de melanoma murino

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Rodrigo Guimaraes

    2012-07-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  15. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2014-09-01

    Full Text Available Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox-treated group. An increase in life span (ILS% = 50.88% was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

  16. Design and preclinical evaluation of melanoma targeting agents for internal radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chezal, J.M.; Papon, J.; Labarre, P.; Denoyer, D.; Bonnet-Duquennoy, M.; Miot-Noirault, E.; Bayle, M.; Chavignon, O.; Teulade, J.C.; Maublant, J.; Madelmont, J.C.; Moins, N. [Centre Jean Perrin, Inserm-Univ. d' Auvergne, UMR 484, 63 - Clermont Ferrand (France)

    2008-02-15

    Targeted internal radionuclide therapy would be an effective alternative to current therapies for disseminated melanoma treatment. N-(2-diethylaminoethyl)-4-iodo benzamide (B.Z.A.) and compounds of this series exhibit a specific affinity for melanoma tissue giving them a potent application for gamma imaging ({sup 123}I) or radionuclide therapy ({sup 131}I or {sup 125}I).With the aim of internal radionuclide therapy, a pharmaco-chemical study has been carried out in order to select new derivatives with a longer retention time in the tumor of melanoma bearing mice and suitable dosimetry. New molecules synthesized are B.Z.A. analogs differing by (1) the aliphatic side chain, (2) aromatic ring. After the design of compounds, the synthesis, and the labelling with {sup 125}I, a study of their biodistribution was performed in B 16 F0 melanoma bearing C.57 B.L.6 mice after i.v. injection. The radioactivity biodistribution was analysed using an A.M.B.I.S.4000 detector on whole body slices of mice obtained by cryo section. The radioactivity was quantified in different organs including tumor and expressed as percentage of injected dose/g of tissue (% I.D./g). Dosimetry parameters for a {sup 131}I utilization were extrapolated using the M.I.R.D. program. The first selected compound has been further evaluated on different models. S.I.M.S. imaging, metabolism and in vivo anti tumoral activity after {sup 131}I labelling were assessed. For number of the studied molecules, a tumor uptake was observed and at least four compounds exhibited an original pharmacokinetic profile: high, specific and durable tumour concentration with a rapid clearance from non-target organs. The tumour concentration after 72 h was increased up to 16- fold compared to B.Z.A. and in term of dosimetry, for a {sup 131}I labelling, the tumor absorbed dose was increased by more than 6-fold. Such profiles made these compounds promising for an application to internal radionuclide therapy. The first selected

  17. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia.

    Science.gov (United States)

    Mar, Victoria; Roberts, Hugh; Wolfe, Rory; English, Dallas R; Kelly, John W

    2013-04-01

    There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  18. Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus.

    Science.gov (United States)

    Pan, Yan; Adler, Nikki R; Wolfe, Rory; McLean, Catriona A; Kelly, John W

    2017-10-16

    To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics. Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne. Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses. Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.

  19. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be effi cient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here ...

  20. Primary malignant melanoma of the nasal cavity.

    Science.gov (United States)

    Uysal, Ismail Önder; Misir, Mustafa; Polat, Kerem; Altuntaş, Emine Elif; Atalar, Mehmet Haydar; Tuncer, Ersin; Müderris, Suphi

    2012-01-01

    Primary malignant melanoma of the nose and paranasal sinus mucosa is a rare disease and seen in less than 1% among all melanomas. Malignant melanomas have 2 origins: cutaneous and mucosal. The mucosal form has a worse prognosis because of its aggressiveness compared with that of the cutaneous form. Mucosal melanomas often occur at a rate of 2% to 3% among all melanomas and are typically found in the nasal cavity and paranasal sinuses. Generally, it is more common in males and in those older than 50 years. In this study, 4 patients were observed at the Cumhuriyet University Faculty of Medicine; 2 of them were a 64-year-old man and an 82-year-old woman who had a malignant melanoma originating from the nasal septal mucosa, 1 patient was a 72-year-old woman whose malignant melanoma originated from the inferior turbinate, and 1 patient was a 77-year-old woman with a sinonasally located melanoma. The conditions of these patients were discussed under the light of literature instructions.

  1. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... ing including positron emission tomography (PET) scan failed to reveal a primary source of malignant melanoma. So, the patient was diagnosed as primary malignant melanoma of aryepiglottic mucosa. Figure 1 Photomicrograph showing origin of melano- ma (H&E, 100x). Figure 2 Photomicrograph ...

  2. Malignant melanoma at a scientific laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-11-15

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs.

  3. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  4. Intraoral malignant melanoma | Babburi | Nigerian Medical Journal

    African Journals Online (AJOL)

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2‑8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and ...

  5. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

    Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

  6. Checkpoint Inhibitors Hold Promise for Rare Melanoma

    Science.gov (United States)

    Patients with a rare form of melanoma, called desmoplastic melanoma, may be particularly likely to benefit from immune checkpoint inhibitors, a new study shows. As this Cancer Currents post explains, an NCI-sponsored clinical trial is already testing one such drug, pembrolizumab (Keytruda) in patients with this cancer.

  7. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  8. Is dermatome shaving a potential treatment for actinic keratosis in organ transplant recipients? A cross-sectional study

    DEFF Research Database (Denmark)

    Kjerkegaard, Ulrik Knap; Bischoff-Mikkelsen, Morten; Damsgaard, Tine Engberg

    2014-01-01

    Background Non-melanoma skin cancer (NMSC) is correlated with high morbidity and mortality in solid-organ transplant recipients (OTR) and it appears after a mean interval of 8 to 10 years. Prophylactic treatments are still required to prevent the development of NMSC. This study aims to investigate...

  9. Sun protective behaviour in renal transplant recipients. A qualitative study based on individual interviews and the Health Belief Model

    DEFF Research Database (Denmark)

    Skiveren, Jette; Mortensen, Erik Lykke; Haedersdal, Merete

    2010-01-01

    BACKGROUND: Renal transplant recipients (RTRs) are at high-risk of developing aggressive and potentially lethal non-melanoma skin cancer, which emphasizes the need for consistent sun protective behaviour. OBJECTIVE: To identify factors that exert an influence on the sun protective behaviour of RTRs...

  10. Organ transplantation from deceased donors with cancer: is it safe?

    Directory of Open Access Journals (Sweden)

    Nalesnik MA

    2011-08-01

    Full Text Available Michael A Nalesnik1, Michael G Ison21Division of Transplantation and Hepatic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburg, PA, USA; 2Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: The availability of donor organs continues to be insufficient to meet the needs of patients actively waiting for transplant. Consequently, there is continuing pressure to increase the donor organ pool while simultaneously assuring safety for the recipient population. The complication of donor malignancy transmission has been documented almost from the beginning of transplantation, and continues to be a concern today. The anecdotal nature of case reports and compiled series ensures that clinical decisions related to organ use from donors with malignancy will of necessity continue to be made on the basis of low-level evidence. Despite this limitation, the literature indicates that not all donor neoplasms have the same risk for transmission to the recipient, and it is necessary to consider the specific malignancy affecting the donor, as well as the condition of the recipient, before a decision is made to transplant or discard a given organ. Published cases suggest that certain forms of neoplasia, such as melanoma, choriocarcinoma, sarcoma, small cell carcinoma, or metastatic carcinomas serve as strong contraindications to organ donation. In contrast, considerable experience exists to suggest that certain tumors of the central nervous system, small subclinical prostate carcinomas, or small renal cell carcinomas resected prior to transplant, among other tumors, should not in themselves disqualify an individual from donating organs in the appropriate circumstance. This review presents the case for considering organ transplantation in the setting of certain donor malignancies and discusses factors to be weighed in such decisions. Additionally

  11. Primary malignant melanoma of aryepiglottic fold | Chhabra | Ghana ...

    African Journals Online (AJOL)

    Background: Primary malignant melanoma rarely arises from noncutaneous tissues that contain melanocytes. Head and neck mucosal melanomas account for 0.7% to 3.8% of all melanomas. Here we report a case of primary malignant melanoma of aryepiglottic fold. Result: Here we reported a case of primary malignant ...

  12. Progression of cutaneous melanoma: implications for treatment

    Science.gov (United States)

    Leong, Stanley P. L.; Mihm, Martin C.; Murphy, George F.; Hoon, Dave S. B.; Kashani-Sabet, Mohammed; Agarwala, Sanjiv S.; Zager, Jonathan S.; Hauschild, Axel; Sondak, Vernon K.; Guild, Valerie; Kirkwood, John M.

    2015-01-01

    The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. PMID:22892755

  13. From Melanocyte to Metastatic Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Bizhan Bandarchi

    2010-01-01

    Full Text Available Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented.

  14. A rare case of rynopharyngeal melanoma

    Directory of Open Access Journals (Sweden)

    Francesco Grecchi

    2012-01-01

    Full Text Available Primary mucosal melanomas (MM of the head and neck region constitute 0.5-2% of all malignant melanomas. The rynopharynx is a region that is less often involved by malignant melanomas. Because most of mucosal melanotic lesions are painless in their early stages, the diagnosis is unfortunately often delayed until symptoms resulting from ulceration, growth, and/or bleeding are noted. Here, we document the rare case of a malignant rynopharynx melanoma of a 43 year old woman. Its treatment and the pertinent literature are discussed. No complication was recorded in the post-operative period and no further surgery was performed. The follow up showed no recurrence in the same position and with the same characteristics, even after six years. Mucosal melanomas are aggressive tumours and the prognosis in these patients is poor. Clinicians must use treatment strategies that provide functional benefit, so as to maintain quality of life without excessive toxicity.

  15. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London University (United Kingdom)

    2010-07-01

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. {sup 211}At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)

  16. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London Univ. (United Kingdom)

    2010-11-15

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. {sup 211}At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (author)

  17. Nanomechanical analysis of pigmented human melanoma cells.

    Science.gov (United States)

    Sarna, Michal; Zadlo, Andrzej; Pilat, Anna; Olchawa, Magdalena; Gkogkolou, Paraskevi; Burda, Kvetoslava; Böhm, Markus; Sarna, Tadeusz

    2013-09-01

    Based on hitherto measurements of elasticity of various cells in vitro and ex vivo, cancer cells are generally believed to be much softer than their normal counterparts. In spite of significant research efforts on the elasticity of cancer cells, only few studies were undertaken with melanoma cells. However, there are no reports concerning pigmented melanoma cells. Here, we report for the first time on the elasticity of pigmented human melanoma cells. The obtained data show that melanin significantly increases the stiffness of pigmented melanoma cells and that the effect depends on the amount of melanin inside the cells. The dramatic impact of melanin on the nanomechanical properties of cells puts into question widely accepted paradigm about all cancer cells being softer than their normal counterparts. Our findings reveal significant limitations of the nanodiagnosis approach for melanoma and contribute to better understanding of cell elasticity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. UVEAL MELANOMA EXTENSION TO THE OPTIC CHIASM.

    Science.gov (United States)

    Abdellatief, Amro; Pulido, Jose S; Bartley, George B; Salomao, Diva R; Quinn, Timothy A

    2016-01-01

    Case report describing a patient who developed intracranial extension of a uveal melanoma through the optic nerve. We reviewed the patient's medical history and images. A 41-year-old woman who was blind in one eye had a uveal melanoma that extended through the optic nerve into the optic chiasm and involved the hypophysis. The patient then developed metastasis. The patient developed uveal melanoma extension into the optic chiasm through the optic nerve resulting in a visual field defect in the fellow eye. Uveal melanoma extension through the optic nerve is a devastating complication, which occurs anywhere from 0.6% to 3.7% in patients with uveal melanoma. If enucleation of the affected eye is performed, a representative portion of the optic nerve should be excised to decrease the risk of extension. Patients with phthisical eyes should undergo appropriate imaging techniques to prevent a missed diagnosis of optic nerve involvement.

  19. Nodular skin melanomas and dermatoscopic diagnostic therein

    Directory of Open Access Journals (Sweden)

    M. V. Zhuchkov

    2016-01-01

    Full Text Available Aim. The study of dermatoscopic pattern characteristics of nodular melanoma with the use of modified Kittler’s pattern analysis. Materials and methods. Clinical and dermatoscopis images of 127 patients with histologically distinctive nodular form of skin melanoma were examined. Nonpolarized dermoscopy of nodular melanoma foci was carried out to patients. Interpretation of obtained dermatoscopic images was performed with the use of pattern analysis modified by Harold Kittler. Main results. The two most important dermatoscopic features of nodular melanoma that distinguish it from other clinical types of this malignant tumor were revealed in our investigation: 1 the prevalence of dermatoscopis images with one pattern (structureless; 2 the prevalence of “grey dots, circles, clods” and “black peripheral dots and clods” as main features of nodular melanoma.

  20. Ab initio investigation of B16(GeS), B27(FeB) and B33(CrB/TlI) phases of lead chalcogenides

    International Nuclear Information System (INIS)

    Demiray, Ferhat; Berber, Savas

    2013-01-01

    We report an ab initio investigation of the intermediate phases occurring in the pressure-induced B1–B2 phase transitions of lead chalcogenides PbX (X = S, Se and Te). The equilibrium lattice constants and atomic positions were calculated without symmetry constraints. The total energies of the optimized structures under pressure were obtained to determine the structures of possible intermediate phases and transitions between these structures. PbTe prefers to be in the B27 structure in the whole transition pressure range while the intermediate phase of PbSe is B27 at lower pressures and becomes B16/B33 at ≈5 GPa. Our results help in understanding the difficulties in experimental investigations of the intermediate phase of PbSe. The intermediate phase of PbS is in the B27 structure at lower pressure values, but it should be in the B16/B33 structure with a transition around ≈6 GPa. Our finding that it is possible to find the intermediate structures of PbS and PbSe in B27 and B16/B33 while PbTe adopts only B27 as the intermediate structure is in good agreement with previous research. The electronic structures of the three structures remain semi-conducting in their calculated optimized structures and the fundamental electronic energy gap decreases with increasing pressure. The projected density of states indicates that the bonding between the Pb atom and the chalcogen has both covalent and ionic contributions with a charge transfer from the Pb atom to the chalcogen. (paper)